Biochemical Society Transactions[JOURNAL]
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200 papers
The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.
Maldonado E, McIsaac E, Ursini-Siegel J
Biochem Soc Trans · 2026 Apr · PMID 42043015 · Full text
Cancer cells face continual stressors, which they must overcome to proliferate and survive in the body. Under these conditions, essential biochemical pathways are disrupted, contributing to various stress responses that...
Cancer cells face continual stressors, which they must overcome to proliferate and survive in the body. Under these conditions, essential biochemical pathways are disrupted, contributing to various stress responses that either promote adaptation and survival or eventual cell death. The evolutionarily conserved integrated stress response (ISR) is a key adaptive mechanism that transiently rewires the transcriptome and translatome in response to various stressors. While the ISR is activated in healthy cells under moderate stress, cancers especially rely on this pathway to overcome harsh conditions experienced during tumor growth and metastasis. We explore the pro-tumorigenic role of the ISR, along with the upstream stress-sensing kinases that activate it. These include protein kinase R-like endoplasmic reticulum kinase, general control non-derepressible 2, double-stranded RNA-dependent protein kinase, and heme-regulated eukaryotic translation initiation factor 2α kinase (HRI), which initiate an ISR in response to diverse stressors by phosphorylating their shared substrate, eukaryotic initiation factor-2α. An in-depth understanding of the pro-survival functions of the ISR and the contexts in which it is pro-tumorigenic is necessary to leverage the ISR as a therapeutic strategy.
The role of HNF4α in adenocarcinoma.
Essel Dadzie H, Snyder EL
Biochem Soc Trans · 2026 Apr · PMID 41925866 · Full text
Hepatocyte nuclear factor 4 alpha (HNF4α) is a conserved nuclear receptor that governs epithelial identity and metabolic homeostasis across endoderm-derived tissues. In cancer, HNF4α can function as either an oncogene or...
Hepatocyte nuclear factor 4 alpha (HNF4α) is a conserved nuclear receptor that governs epithelial identity and metabolic homeostasis across endoderm-derived tissues. In cancer, HNF4α can function as either an oncogene or a tumor suppressor. In colorectal and hepatocellular carcinoma, reduced HNF4α activity accompanies loss of differentiation and tumor progression, consistent with tumor-suppressive functions. In contrast, in pancreatic ductal adenocarcinoma, invasive mucinous adenocarcinoma, and other lineage-defined epithelial tumors, HNF4α can also participate in transcriptional programs that sustain malignant identity, metabolic adaptation, and therapeutic resistance. However, these effects are highly context-dependent and do not imply a uniformly oncogenic role in these tumor types. These divergent functions are shaped by isoform usage, chromatin state, epigenetic regulation, metabolic cues, and transcription factor networks. Rather than acting as a classical oncogene or tumor suppressor in all settings, HNF4α is better understood as a context-dependent regulator of lineage state whose activity may either restrain tumor progression or support tumor maintenance. This mini review highlights the molecular mechanisms that shape HNF4α activity, including isoform biology and epigenetic control, and discusses emerging strategies for selectively inhibiting HNF4α in dependency states or restoring its differentiation-promoting functions in tumors where it is lost.
Advances in polarised luminescence approaches to understanding interactions between biomolecules.
Habel E, Vishwakarma P, Huber T … +1 more , Rodger A
Biochem Soc Trans · 2026 Apr · PMID 41925201 · Full text
Luminescence spectroscopies are attractive due to their sensitivity and selectivity. Polarised light provides added dimensions to luminescence data, leading to techniques that provide information about molecular structur...
Luminescence spectroscopies are attractive due to their sensitivity and selectivity. Polarised light provides added dimensions to luminescence data, leading to techniques that provide information about molecular structure and interactions. In this review the principles of steady-state fluorescence techniques, including fluorescence-detected circular dichroism, fluorescence-detected linear dichroism, fluorescence polarisation anisotropy, circularly polarised luminescence, and linearly polarised luminescence, are outlined and illustrated with examples of how they have been used to study biomolecules and their interactions with other molecules.
Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.
Cieslicka J, Pianka K, Drazkowska K … +1 more , Sikorski PJ
Biochem Soc Trans · 2026 Mar · PMID 41873699 · Full text
Double-stranded RNA (dsRNA) is a universal indicator of viral replication and dysregulated RNA metabolism. Detection of dsRNA triggers some of the most powerful innate immune responses in human cells. Although these mole...
Double-stranded RNA (dsRNA) is a universal indicator of viral replication and dysregulated RNA metabolism. Detection of dsRNA triggers some of the most powerful innate immune responses in human cells. Although these molecules differ in origin and structure, viral dsRNAs share the defining geometric and electrostatic features of the A-form helix, enabling their sequence-independent recognition by multiple sensor systems. Cytosolic receptors, like retinoic acid-inducible gene I (RIG-I), melanoma differentiation associated gene 5 (MDA5), and protein kinase R (PKR), as well as the oligoadenylate synthase (OAS)/RNase L pathway, convert dsRNA binding into interferon induction, translational arrest, and widespread RNA decay, while endosomal Toll-like receptor 3 (TLR3) and the inflammasome sensor NLR family pyrin domain containing 1 (NLRP1) expand surveillance to internalised or structurally disruptive RNAs. Counterbalancing these pathways, the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) marks endogenous dsRNA through A-to-I conversion, preventing inadvertent activation of innate immune response and maintaining self versus non-self discrimination. Although all of these sensors recognise the A-form helix, each extracts distinct structural and chemical information from dsRNA and converts it into a specific response: RIG-I detects short duplexes with 5'-triphosphorylated ends; MDA5 assembles cooperatively along long uninterrupted helices; PKR integrates duplex length with translational control; OAS proteins act as strict reporters of helix regularity; and TLR3 as well as NLRP1 respond to dsRNA in compartment- and context-dependent ways. Epitranscriptomic marks and chemical modifications-including 2'-O-methylation, N6-methyladenosine, pseudouridine, and ADAR1-mediated inosine-further refine sensing by modulating helical stability and end structure, establishing a biochemical 'self-code' that shapes RNA immunogenicity. Together, these pathways form an integrated network that distinguishes between viral and endogenous dsRNA and coordinates antiviral defence with immune tolerance.
Reprogramming the inactive X chromosome: dynamics and insights from the germline.
Moyano Rodriguez Y, Borensztein M
Biochem Soc Trans · 2026 Mar · PMID 41873698 · Full text
Germline reprogramming is an essential process that resets the epigenome prior to gamete formation. Primordial germ cells (PGCs), the progenitors of oocytes and spermatozoa, undergo extensive epigenetic remodelling durin...
Germline reprogramming is an essential process that resets the epigenome prior to gamete formation. Primordial germ cells (PGCs), the progenitors of oocytes and spermatozoa, undergo extensive epigenetic remodelling during development, including genome-wide DNA demethylation, histone modification remodelling, and large-scale reorganisation of 3D genome architecture. In female mammals, an additional layer of epigenetic regulation occurs during PGC reprogramming: the reactivation of the inactive X chromosome, namely, X-chromosome reactivation (XCR). Female PGC precursors carry an inactive X chromosome to ensure dosage compensation prior to reprogramming. While X-chromosome inactivation has been extensively studied for decades, XCR has only more recently emerged as a focus of investigation, and its functional importance for germline development and reproduction remains unclear. XCR takes place along PGC differentiation, from early emergence to meiosis, and involves loss of the long non-coding RNA XIST/Xist coating, DNA demethylation at X-linked promoters, and re-expression of X-linked genes from the inactivated X. Sequential molecular events occurring during XCR have been characterised using both in vivo and in vitro approaches in a broad range of mammals from rodents to humans. In recent years, the emergence of low-input and single-cell omics technologies has substantially advanced our understanding of the inactive X-chromosome reactivation in the germline. In this review, we synthetise recent insights into XCR dynamics in mouse, human, and non-human primate PGCs. We discuss the remaining knowledge gaps and the future perspectives in the field of XCR and germline epigenetic reprogramming.
Breaking cellular boundaries: molecular mechanisms of tunneling nanotube formation and fusion.
Belian S, Zurzolo C
Biochem Soc Trans · 2026 Mar · PMID 41823589 · Full text
Tunneling nanotubes (TNTs) are thin, actin-based membrane bridges that establish direct cytoplasmic continuity between distant cells, enabling the transfer of diverse cargoes ranging from ions and proteins to organelles...
Tunneling nanotubes (TNTs) are thin, actin-based membrane bridges that establish direct cytoplasmic continuity between distant cells, enabling the transfer of diverse cargoes ranging from ions and proteins to organelles such as mitochondria. Since their discovery in 2004, TNTs have been identified in numerous cell types and linked to an expanding range of physiological and pathological functions. Yet, their molecular identity and mechanisms of formation remain elusive. The most defining and least understood step in TNT biogenesis is membrane fusion, the process by which TNTs achieve open-ended continuity between cells, and this represents a critical frontier in the field. This review integrates recent advances in TNT biology, emphasizing the interplay between actin cytoskeletal dynamics, plasma membrane composition, and cell adhesion during TNT formation. It also draws mechanistic parallels with established models of membrane fusion, highlighting fundamental principles and shared regulators across fusion systems, many of which have been implicated in TNT functionality. By combining molecular, biophysical, and imaging perspectives, this review proposes a conceptual framework for TNT formation and fusion, identifies major methodological gaps, and outlines future directions to unravel the mechanisms that underlie intercellular cytoplasmic continuity.
Methods for studying the effects of phosphorylation patterns in proteins.
Bressler SG, Grunhaus D, Hurevich M … +1 more , Friedler A
Biochem Soc Trans · 2026 Mar · PMID 41823588 · Full text
Protein phosphorylation is one of the most common and versatile regulatory mechanisms in cells. Most human proteins are phosphorylated at multiple sites, giving rise to large numbers of possible phosphorylation patterns....
Protein phosphorylation is one of the most common and versatile regulatory mechanisms in cells. Most human proteins are phosphorylated at multiple sites, giving rise to large numbers of possible phosphorylation patterns. Each phosphorylation pattern can lead to a different functional or pathological outcome. Yet, linking defined phosphorylation patterns to specific biological functions remains a major experimental challenge. In this review we describe the main strategies to study phosphorylation patterns at the protein and domain levels and highlight how they complement each other. We first discuss cellular approaches, including phosphomimetics, kinase-based assays, and genetic code expansion, which allow working in a native environment but have their significant drawbacks. We then describe in vitro methods, such as enzymatic phosphorylation and semi-synthetic phosphoproteins generated by ligation, which afford mechanistic insights but result in low yields and are difficult to scale for producing libraries. We focus on synthetic phosphopeptide libraries as tools that offer precise control over the number and position of phosphosites and are uniquely suited for systematic mapping of phosphorylation patterns. This comes at a price of not working at the protein level, but rather at the domain level. Peptide libraries are often used for preliminary identification of key phosphorylations, later studied in detail at the protein level. We conclude that ideally more than one method should be used and that these methods should not be viewed as competing but rather as complementary. A combined use of several of these approaches provides a practical toolbox for dissecting how phosphorylation patterns regulate protein behavior.
Heme oxygenase-like dimetal oxidases and oxygenases.
Skirboll SS, Ledinina AE, Makris TM
Biochem Soc Trans · 2026 Mar · PMID 41823132 · Full text
The first heme oxygenase-like dimetal oxidase/oxygenase (HDO) was functionally validated through coordinated spectroscopic and rapid kinetic studies of the fatty acid decarboxylase UndA. The enzyme superfamily has since...
The first heme oxygenase-like dimetal oxidase/oxygenase (HDO) was functionally validated through coordinated spectroscopic and rapid kinetic studies of the fatty acid decarboxylase UndA. The enzyme superfamily has since been recognized to orchestrate a variety of substrate transformations for natural product biosynthesis. In this mini-review, we report on the structures and the catalytic mechanisms of the major HDO subtypes that catalyze carbon-carbon bond cleavage, N-oxygenation, multi-step rearrangements, and radical hole-hopping. A summary of the current status of the field and opportunities for decrypting the molecular basis for the mechanistic divergence of the family are highlighted.
The segregation of organelles and organellar genomes across eukaryotic biology.
Jetishi C, Gerber M, Ochsenreiter T
Biochem Soc Trans · 2026 Mar · PMID 41823131 · Full text
Eukaryotic cells are characterized by the presence of organelles such as mitochondria and, in the case of plants and certain protists, plastids, both of which often contain their own genomes. Accurate distribution of rep...
Eukaryotic cells are characterized by the presence of organelles such as mitochondria and, in the case of plants and certain protists, plastids, both of which often contain their own genomes. Accurate distribution of replicated organelles and their genomes to daughter cells is crucial for cell survival and propagation across all eukaryotic organisms. Unlike nuclear DNA, which follows a well-characterized segregation process via the mitotic spindle, organelle genomes are inherited through more diverse and less-understood mechanisms. Ensuring proper organelle genome inheritance is essential for maintaining cellular energy production, metabolic functions, and overall viability. Because organelle and organelle genome segregation lack a universal mechanism, different organisms employ various strategies that include stochastic distribution and active cytoskeletal transport and membrane tethering to prevent the loss of essential genetic material while supporting organelle division and turnover. This review provides an overview of organelle and organellar DNA segregation mechanisms in diverse eukaryotic systems before focusing on the tripartite attachment complex as a specialized adaptation in kinetoplastid parasites.
Disruption of BDNF signalling in neuropathologies.
Paulo-Ramos A, Rhymes ER, Villarroel-Campos D … +1 more , Sleigh JN
Biochem Soc Trans · 2026 Feb · PMID 41729684 · Full text
The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities...
The vital role of brain-derived neurotrophic factor (BDNF) in neuronal development, synaptic plasticity, and neuroprotection has been explored for decades. Therefore, the expression, processing, and signalling activities of this neurotrophin, which is reliant upon TrkB and p75NTR receptors, have been well characterised in both health and disease. This review summarises the latest findings on BDNF dysregulation in neuropathologies. Indeed, across diseases of both the central and peripheral nervous systems, BDNF signalling is frequently disrupted, contributing to neuronal dysfunction and degeneration. Consequently, through direct or indirect enhancement of its expression and/or function, BDNF has proved to be a promising therapeutic target across many neurological conditions. However, the complexity of its regulation and interaction with several different receptors underpins the need for further research to deepen our understanding of BDNF disruption in neuropathologies and to achieve its therapeutic potential.
Emerging liquid biopsy tools to analyse cancer biomarkers: electrochemical sensors and extracellular vesicle analysis.
Devadoss A, Furness MR, Wu NJW … +3 more , Oikonomidou O, Kersaudy-Kerhoas M, Leslie NR
Biochem Soc Trans · 2026 Feb · PMID 41705305 · Full text
Better biomarker analysis technologies can provide improvements in the detection, characterisation and monitoring of cancer and less invasive sampling of blood and other body fluids can improve acceptability and affordab...
Better biomarker analysis technologies can provide improvements in the detection, characterisation and monitoring of cancer and less invasive sampling of blood and other body fluids can improve acceptability and affordability. Here, we discuss these technologies with a specific focus on recent advances in electrochemical sensors, specifically for the analysis of extracellular vesicles (EVs). Widely used biomarker tests with relatively high sensitivity (e.g. ELISAs) are limited by their cost, storage requirements and shelf-life, and ease of use away from centralised facilities. Moreover, their limits of detection (most commonly in the nanomolar to picomolar, with new technologies pushing into the femtomolar range) remain challenged by low abundance biomarkers. Here, we discuss how electrochemical sensor platforms, although often requiring more effort to adapt for new analytes, can provide high sensitivity and direct quantitation at low cost. These platforms are also often simpler to use away from testing facilities. Additionally, we explore how EVs, by protecting nucleic acid and protein cargos from degradation, may facilitate the collective enrichment from blood samples of multiple tumour-derived biomarkers. Continued progress in analysis technologies, alongside a deeper understanding of biomarker biology and clinical value, holds the potential to improve outcomes for the increasing numbers of individuals diagnosed with cancer.
Human iPSCs: atrial versus ventricular cardiomyocytes and their functional and pharmacological differences.
Broadbent SD, Bhagwan JR, Olusoga T … +1 more , Barnes A
Biochem Soc Trans · 2026 Feb · PMID 41700750 · Full text
The continuing development and characterisation of human-induced pluripotent stem cell (hiPSC)-derived cell-types has opened up a virtually endless source of human, physiologically relevant cells, available at scale, for...
The continuing development and characterisation of human-induced pluripotent stem cell (hiPSC)-derived cell-types has opened up a virtually endless source of human, physiologically relevant cells, available at scale, for scientific research. The technology's maturation and refinement have allowed additional cell-types and sub-types to become available. The first step in adopting these novel cell-types is to properly characterise these cells and compare how they perform against the longer-established cell-types. Parallel to the progress in iPSC-derived cells has been the great strides in the platforms developed to assess and analyse the characteristics and functions of cells. These improved platforms have greatly increased the range, throughput and quality of the functional data that can be obtained from cell-types, including iPSC-derived cells. Research into cardiomyocytes in particular has been greatly enhanced by these platforms as cardiomyocytes not only have the expected cellular markers, proteomics and transcriptomics but are also electrically active and capable of contracting, opening a wide vista of potential assays. If human iPSC-derived cardiomyocytes are to confidently replace and supplement the existing animal and cellular models of the heart, it has to be demonstrated that they correctly replicate (or even improve) upon the functions and pharmacology of the existing heart models used on these new and improved platforms. Therefore, this review compares the functional and pharmacological differences seen between Axol's human iPSC-derived atrial and ventricular cardiomyocyte cells on a range of established and newer platforms demonstrating the advantages of using chamber-specific human iPSC-derived cardiomyocytes and discussing how their use could supplement these emerging techniques.
Designing de novo TIM barrels: insights into stabilization, diversification, and functionalization strategies.
Beck J, Romero-Romero S
Biochem Soc Trans · 2026 Feb · PMID 41669938 · Full text
The triosephosphate isomerase (TIM)-barrel fold is one of the most versatile and ubiquitous protein folds in nature, hosting a wide variety of catalytic activities and functions while serving as a model system in protein...
The triosephosphate isomerase (TIM)-barrel fold is one of the most versatile and ubiquitous protein folds in nature, hosting a wide variety of catalytic activities and functions while serving as a model system in protein biochemistry and engineering. This review explores its role as a key fold model in protein design, particularly in addressing challenges in stabilization and functionalization. We discuss historical and recent advances in de novo TIM barrel design from the landmark creation of sTIM11 to the development of the diversified variants, with a special focus on deepening our understanding of the determinants that modulate the sequence-structure-function relationships of this architecture. Also, we examine why the diversification of de novo TIM barrels toward functional diversification remains an open problem, given the absence of natural-like active site features. Current approaches have focused on incorporating structural extensions, modifying loops, and using cutting-edge AI-based strategies to create scaffolds with tailored characteristics. Despite significant advances, achieving enzymatically active de novo TIM barrels has been proven difficult, with only recent breakthroughs demonstrating functional activity. We discuss the limitations of stepwise design approaches and support integrated strategies that simultaneously optimize scaffold structure and active site shape, using both physics-based and AI-driven methods. By combining computational and experimental insights, we highlight the TIM barrel as a powerful template for custom enzyme design and as a model system to explore the intersection of protein biochemistry, biophysics, and design.
Poxviral Bcl-2 proteins: multifunctional manipulators of the host cell.
Smyth S, Dong J, Melvie G … +1 more , Ingham RJ
Biochem Soc Trans · 2026 Feb · PMID 41649038 · Publisher ↗
Poxviruses are double-stranded DNA viruses that infect a wide range of animals. Their large genomes encode for over 200 proteins and many of these help establish infection by inhibiting cell death or interfering with hos...
Poxviruses are double-stranded DNA viruses that infect a wide range of animals. Their large genomes encode for over 200 proteins and many of these help establish infection by inhibiting cell death or interfering with host antiviral signalling pathways. This includes the poxviral B cell lymphoma-2 (Bcl-2) proteins, which are found in most of the Chordopoxvirinae (vertebrate-infecting poxviruses), with individual viruses possessing multiple Bcl-2 proteins. These proteins are so named for the fact that they adopt an alpha helical bundle with structural similarity to cellular anti-apoptotic Bcl-2 proteins, despite lacking obvious primary amino acid sequence identity with these proteins. Not surprisingly, initial studies found that some poxviral Bcl-2 proteins inhibit apoptosis; however, it was soon clear that these proteins have additional functions. This brief review highlights some of these other activities that have either been more recently identified or for which additional mechanistic insight has been acquired. This includes the role of poxviral Bcl-2 proteins in modulating nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein (NLRP) inflammasome activation and inhibiting antiviral signalling regulated by the interferon regulatory factor 3 and 7 (IRF3/7) transcription factors. Finally, we discuss how poxviral Bcl-2 proteins interfere with cellular antiviral TRIM family E3 ubiquitin-ligases to promote virus replication.
DNA translocation by the CMG helicase: the helical inchworm model.
Batra S, Allwein B, Wang YL … +2 more , Hite RK, Remus D
Biochem Soc Trans · 2026 Feb · PMID 41649037 · Full text
In all cells, hexameric helicases drive the unwinding of parental chromosomal DNA at replication forks to provide the single-stranded DNA templates required by replicative DNA polymerases. DNA unwinding proceeds via a st...
In all cells, hexameric helicases drive the unwinding of parental chromosomal DNA at replication forks to provide the single-stranded DNA templates required by replicative DNA polymerases. DNA unwinding proceeds via a steric exclusion mechanism in which the helicase encircles and translocates along one DNA strand while sterically excluding the opposite strand from its central channel. The details of how hexameric helicases translocate on single-stranded DNA remain incompletely understood and likely vary among species, as structural and mechanistic features-such as motor domain architecture and translocation polarity-shape helicase function. Recent high-resolution cryo-EM structures of the eukaryotic CMG (Cdc45-MCM-GINS) helicase, including complexes stalled at leading-strand G-quadruplexes, reveal two predominant DNA-bound conformations: planar and spiral. These structures show that different subsets of MCM subunits alternately engage the leading-strand template, defining intermediates of a nonrotary, hand-over-hand translocation mechanism. This mode of translocation differs from the sequential rotary hand-over-hand mechanism proposed for bacterial hexameric helicases, instead resembling that of other ring-shaped ATPase motors and can be described as a variant of the helical inchworm model. The evolution of this mechanism may reflect CMG's specialized role as a replisome organizer, enabling it to coordinate accessory factors and optimize replication fork progression. Together, these findings highlight the mechanistic diversity and evolutionary adaptability of hexameric helicases.
Correction: The application of single-molecule optical tweezers to study disease-related structural dynamics in RNA.
Marinus T, Foster T, Tych K
Biochem Soc Trans · 2026 Feb · PMID 41640177 · Full text
Abstract loading — click title to view on PubMed.
Plasticity and stringency: rethinking stem cell division modes.
Bener MB, Inaba M
Biochem Soc Trans · 2026 Feb · PMID 41626805 · Full text
Asymmetric cell division (ACD) has been extensively studied in various stem cell systems as a fundamental mechanism that ensures the balance between stem cell self-renewal and differentiation. ACD allows one daughter cel...
Asymmetric cell division (ACD) has been extensively studied in various stem cell systems as a fundamental mechanism that ensures the balance between stem cell self-renewal and differentiation. ACD allows one daughter cell to retain stem cell identity while the other commits to differentiation, thereby maintaining tissue homeostasis over time. Stem cells also undergo symmetric cell division, in which both daughter cells adopt either stem or differentiated fates. What are the outcomes of each cell division mode, and how strictly are these modes executed across different stem cell systems? There have been technical challenges of visualizing stem cell division in vivo due to the structural complexity of tissues and the rarity and ambiguous identity of genuine stem cells. Despite these difficulties, recent technical advancements have revealed how these cells operate within their native environments. This review summarizes key studies that elucidate distinct division modes and their functional outcomes across various stem cell systems.
Microtubule inner proteins in apicomplexan parasites.
Binder AM, Frischknecht F, Hentzschel F
Biochem Soc Trans · 2026 Feb · PMID 41626803 · Full text
Microtubule inner proteins (MIPs) are integral components within the microtubule lumen of various organisms, contributing to microtubule structural integrity and functionality. Apicomplexan parasites, including Plasmodiu...
Microtubule inner proteins (MIPs) are integral components within the microtubule lumen of various organisms, contributing to microtubule structural integrity and functionality. Apicomplexan parasites, including Plasmodium spp. and Toxoplasma gondii, exhibit a range of specialized tubulin structures, such as axonemal microtubules, subpellicular microtubules (SPMTs), and conoid fibers, playing critical roles in cellular morphology and motility. Yet, in contrast with model organisms, only a few MIPs have been characterized in apicomplexans so far. Recent advances in cryo-electron tomography and structural proteomics have facilitated the study of MIPs, shedding light on unique adaptations that distinguish apicomplexan microtubules from those in model eukaryotes. Key findings include the identification of an interrupted luminal helix in SPMTs, which is critical for stabilizing microtubules under stress. The relatively small repertoire of axonemal MIPs contrasts markedly with the numerous MIPs observed in other systems, possibly reflecting adaptations for rapid microtubule assembly without intraflagellar transport. Furthermore, emerging evidence points to multiple MIPs within the conoid and SPMTs, suggesting further roles for MIPs in these parasites. This review highlights the currently known contributions of MIPs to the survival and proliferation of these parasites, while emphasizing the need for continued research to fully characterize their diverse roles and molecular mechanisms.
Advances in understanding Ton and Tol system motor proteins.
Celia H, Buchanan SK, Botos I
Biochem Soc Trans · 2026 Jan · PMID 41615764 · Full text
The Ton and Tol-Pal systems are molecular machines that are essential for survival of Gram-negative bacteria.Both use the energy derived from the proton gradient at the inner membrane to generate force on protein compone...
The Ton and Tol-Pal systems are molecular machines that are essential for survival of Gram-negative bacteria.Both use the energy derived from the proton gradient at the inner membrane to generate force on protein components at the outer membrane. Ton and Tol share extensive homology, but they fulfill different functions: Ton is involved in the active transport of essential nutrients from the extracellular media into the cell, while Tol maintains the outer membrane integrity and participates in the cell division process. Despite decades of biochemical and biophysical studies, the molecular mechanism coupling the proton gradient at the inner membrane with the propagation of force and movement to the outer membrane is not understood. In this review, we discuss the recent high-resolution structures obtained for both systems, and how these structures fit with existing mechanistic models.
Mechanisms of transcriptional regulation of CCR5, which is the co-receptor for R5-tropic HIV and is also involved in other disease processes.
Wang L, Akisa SV, Sutton R
Biochem Soc Trans · 2026 Jan · PMID 41608770 · Full text
C-C chemokine receptor type 5 (CCR5) is the R5-tropic human immunodeficiency virus type 1 or HIV co-receptor. Lower CCR5 levels can reduce T cell and macrophage susceptibility and suppress HIV infection. Moreover, CCR5Δ3...
C-C chemokine receptor type 5 (CCR5) is the R5-tropic human immunodeficiency virus type 1 or HIV co-receptor. Lower CCR5 levels can reduce T cell and macrophage susceptibility and suppress HIV infection. Moreover, CCR5Δ32 homozygous stem cell transplantation is central to HIV cure. Other studies have shown that CCR5 plays a vital role in cancer development and cell migration, and it was considered a potential therapeutic target for several types of malignancy. In addition to HIV and cancer, CCR5 also participates in immune response and plays a role in graft-versus-host disease in bone marrow transplant patients. It is also associated with other diseases, such as Parkinson's disease and rheumatoid arthritis. Thus, investigating its regulatory mechanisms is critically important for understanding the progress and therapeutics of other illnesses. Transcriptional regulation of genes is a complex process that controls when, where, and how much the RNA transcript is produced. In this minireview, we discuss epigenetic regulatory mechanisms, such as DNA methylation and histone modification, transcription factors, and signal transduction pathways, involved in the regulation of CCR5 transcripts.
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