Biochemical Society transactions最新文献

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RNA-binding protein hnRNPK: a multifunctional regulator of skeletal muscle biology and disease. rna结合蛋白hnRNPK:骨骼肌生物学和疾病的多功能调节剂。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250557
Kejin Ren, Kaili Zhou, Yijia An, Xiaofang Cheng, Tiantian Meng, Cencen Li, Haixia Xu, Pengpeng Zhang, Yongjie Xu
{"title":"RNA-binding protein hnRNPK: a multifunctional regulator of skeletal muscle biology and disease.","authors":"Kejin Ren, Kaili Zhou, Yijia An, Xiaofang Cheng, Tiantian Meng, Cencen Li, Haixia Xu, Pengpeng Zhang, Yongjie Xu","doi":"10.1042/BST20250557","DOIUrl":"10.1042/BST20250557","url":null,"abstract":"<p><p>Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a highly conserved, multifunctional DNA/RNA-binding protein that regulates gene expression at both transcriptional and post-transcriptional levels. In skeletal muscle, hnRNPK is essential for development, regeneration, and homeostasis, influencing satellite cell activation, myoblast proliferation and differentiation, and myofiber maturation. Its dysregulation is linked to muscle atrophy, degenerative diseases, and impaired regeneration. This review summarizes current knowledge of hnRNPK's molecular structure, subcellular localization and dynamics, and interactions with nucleic acids and proteins. We highlight its roles in myogenic differentiation, gene expression control, signaling pathway cross-talk, and skeletal muscle development. We also discuss the potential of hnRNPK as a diagnostic biomarker and therapeutic target in muscle disorders, and outline key directions for future research to resolve outstanding questions about its complex regulatory functions. Together, these insights provide a framework for advancing muscle biology and improving the management of muscle-related diseases.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"571-584"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TAM receptor tyrosine kinases as potential mediators of the non-lytic spread of non-enveloped viruses. TAM受体酪氨酸激酶作为非包膜病毒非溶性传播的潜在介质。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250119
Steven J Moran, Chrystal A Starbird
{"title":"TAM receptor tyrosine kinases as potential mediators of the non-lytic spread of non-enveloped viruses.","authors":"Steven J Moran, Chrystal A Starbird","doi":"10.1042/BST20250119","DOIUrl":"10.1042/BST20250119","url":null,"abstract":"<p><p>Tyro3, Axl, and Mer are receptor tyrosine kinases that comprise the TAM receptor family. These receptors, originally identified as orphan receptors, do not bind growth factors but rather ligands that can facilitate processes such as phagocytosis and dampening the innate inflammatory immune response. Enveloped viruses can hijack TAM receptors for viral entry through the fairly well-established mechanism of apoptotic mimicry. This mechanism involves 'tricking' the targeted host cell into endocytosing the virus through binding to exposed phosphatidylserine in the viral lipid bilayer envelope. While enveloped viruses utilize apoptotic mimicry for entry, it remains unclear how non-enveloped viruses enter the host cell through phosphatidylserine receptors such as TAM receptors. There is evidence that non-enveloped viruses can usurp host cell signaling pathways to cloak their particles in membranes, creating 'quasi-enveloped' viruses that enter the host through a sort of 'faux apoptotic mimicry.' These quasi-enveloped viruses can spread through non-lytic mechanisms to evade the host immune response and deliver virus particles to the targeted host cell. With the present review, we evaluate increasing evidence that TAM receptors may play a role in this process through their ability to indiscriminately bind phosphatidylserine in membranes, leading to the internalization of non-enveloped viruses packaged within phosphatidylserine-enriched extracellular vesicles.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"501-512"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanistic insight into the oxidative degradation of monoclonal antibodies: relevance to developability and the design of stable pharmaceutical formulations. 单克隆抗体氧化降解的机制洞察:与可开发性和稳定药物配方的设计相关。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250134
Christian Schöneich
{"title":"Mechanistic insight into the oxidative degradation of monoclonal antibodies: relevance to developability and the design of stable pharmaceutical formulations.","authors":"Christian Schöneich","doi":"10.1042/BST20250134","DOIUrl":"10.1042/BST20250134","url":null,"abstract":"<p><p>Oxidation represents a key pathway for the chemical degradation of therapeutic monoclonal antibodies (mAbs), and chemical liabilities such as amino acid residue oxidation are an integral part of developability studies. Mechanistically, oxidation reactions in formulations of therapeutic mAbs are frequently not well understood, as critical information such as the nature of the oxidant(s) is frequently lacking. This brief review summarizes recent screening and developability studies of therapeutic proteins specifically focusing on oxidative liabilities and discusses these data in view of mechanistic and complementary analytical information on the oxidation of amino acid residues in specific protein sequences.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"523-533"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural insights into HRI kinase activity and inhibition. HRI激酶活性和抑制的结构见解。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250541
Min Cao, Glenn R Masson
{"title":"Structural insights into HRI kinase activity and inhibition.","authors":"Min Cao, Glenn R Masson","doi":"10.1042/BST20250541","DOIUrl":"10.1042/BST20250541","url":null,"abstract":"<p><p>Haem-regulated inhibitor (HRI) is emerging as a potential therapeutic target in several disease areas, including cancers such as multiple myeloma and neurodegenerative disease. As one of four related mammalian kinases that phosphorylate the mRNA translation machinery substrate eIF2α, it has a central role in sensing several disparate proteotoxic stresses and preventing subsequent rounds of protein production. In this review, we will examine the latest research on the structural and molecular basis of HRI inhibition and activation, examining both regulatory biological interactions with proteins and cofactors. What emerges is that despite almost 75 years since the first identification of HRI, we still know remarkably little about how this kinase functions and is regulated.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"561-569"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Native mass spectrometry meets X-rays for the elucidation of protein structures. 原生质谱法符合x射线的蛋白质结构的阐明。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250111
Thomas Kierspel, Emiliano de Santis, Kira Schamoni-Kast, Clement Blanchet, Erik G Marklund, Carl Caleman, Charlotte Uetrecht
{"title":"Native mass spectrometry meets X-rays for the elucidation of protein structures.","authors":"Thomas Kierspel, Emiliano de Santis, Kira Schamoni-Kast, Clement Blanchet, Erik G Marklund, Carl Caleman, Charlotte Uetrecht","doi":"10.1042/BST20250111","DOIUrl":"10.1042/BST20250111","url":null,"abstract":"<p><p>Small-angle X-ray scattering (SAXS) is a powerful and widely used technique for structural biology, providing information about solution structures, i.e., without the need for crystallization or cryogenic conditions. However, its applicability is limited in cases where sample heterogeneity, conformational mixtures, or aggregation are present. While modern BioSAXS routinely employs inline purification (e.g., SEC-SAXS) to address heterogeneity, gas-phase SAXS, enabled by native mass spectrometry as a sample delivery method, offers an even higher degree of population selectivity by providing well-defined and mass-selected ion populations. The principal challenge of this approach is the inherently low particle density in the gas phase. In the present overview, we present simulations of gas-phase SAXS viral nonstructural proteins and capsids and compare them against diffraction patterns from prototypical GroEL. We evaluate the expected scattering signal under experimentally realistic conditions and discuss potential implementations and use cases at both synchrotron radiation sources and X-ray free-electron lasers, thereby outlining regimes in which gas-phase SAXS may become a viable complementary tool for structural studies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"513-521"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MGRN1 in development and disease: a unifying view of a versatile membrane-tethered E3 ubiquitin ligase. MGRN1在发育和疾病中的作用:一种多功能膜系E3泛素连接酶的统一观点。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250109
Alyssa Riglos, Teresa M Gunn, Jennifer H Kong
{"title":"MGRN1 in development and disease: a unifying view of a versatile membrane-tethered E3 ubiquitin ligase.","authors":"Alyssa Riglos, Teresa M Gunn, Jennifer H Kong","doi":"10.1042/BST20250109","DOIUrl":"10.1042/BST20250109","url":null,"abstract":"<p><p>Mahogunin Ring Finger 1 (MGRN1) is a multifunctional E3 ubiquitin ligase with broad biological significance and belongs to a small group of membrane-tethered E3s capable of regulating signaling receptors at the plasma membrane. Studies in mice first revealed its physiological importance, as loss of Mgrn1 leads to a wide range of phenotypes, including abnormal pigmentation, congenital malformations, and neurodegeneration. Remarkably, MGRN1 localizes to multiple cellular compartments, including the plasma membrane, mitochondria, nucleus, and endo-lysosomal pathway. MGRN1 is also involved in several cellular processes, including receptor regulation, protein homeostasis, and mitochondrial maintenance. While studies have emphasized the importance of MGRN1, it has been difficult to define unifying principles governing its function. In the present review, we summarize and integrate published findings to develop a clearer picture of MGRN1's roles, focusing on phenotypes observed in mouse models and the signaling pathways MGRN1 regulates. We propose shared mechanistic themes that reconcile the functional diversity of this unique E3 ligase, highlight gaps in the current literature, and identify areas for further investigation to better understand MGRN1's role in disease and evaluate its potential relevance for targeted protein degradation strategies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"449-460"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities. Rho GTPases在抗癌中的作用:机制、脆弱性和治疗机会。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250097
Amy Beaudin, Philippe Lefrançois, Mélanie Laurin
{"title":"Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.","authors":"Amy Beaudin, Philippe Lefrançois, Mélanie Laurin","doi":"10.1042/BST20250097","DOIUrl":"10.1042/BST20250097","url":null,"abstract":"<p><p>Intrinsic and adaptive resistance to therapy remain major barriers to effective cancer treatment. Diverse resistance mechanisms, including epithelial-mesenchymal transition, enhanced tolerance to DNA damage, impaired cell death pathways, metabolic reprogramming, and cues from the tumour microenvironment, are increasingly recognised as being tightly integrated with Rho GTPase signalling networks. Accumulating evidence positions these pathways as central regulators of therapeutic resistance across multiple cancer types. In this review, we synthesise recent experimental findings linking Rho GTPase-mediated signalling to therapy resistance and evaluate emerging strategies aimed at targeting these signalling axes. We critically examine the translational readiness of approaches that directly inhibit Rho GTPases, disrupt downstream effector pathways, or modulate canonical regulators such as RhoGEFs and RhoGAPs, and discuss the key challenges and opportunities associated with their clinical deployment. Collectively, these insights highlight the therapeutic potential of targeting Rho GTPase signalling as a foundation for next-generation cancer treatments.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"461-476"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
G0 or no-G0: phosphatase control of quiescence and cell cycle entry. G0或no-G0:静止和细胞周期进入的磷酸酶控制。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250091
Eleanor A Robinson, Alexis R Barr
{"title":"G0 or no-G0: phosphatase control of quiescence and cell cycle entry.","authors":"Eleanor A Robinson, Alexis R Barr","doi":"10.1042/BST20250091","DOIUrl":"10.1042/BST20250091","url":null,"abstract":"<p><p>During each cell cycle, cells must decide whether to continue to proliferate or to exit the cell cycle into a reversible arrest state, known as quiescence, or G0. This decision must be highly regulated to ensure proper tissue homeostasis. Studies on kinase-driven signalling pathways that regulate this decision point have dominated the field, and the role of phosphatases remains comparatively underexplored, yet the role of phosphatases is vitally important in signal transduction. In the present review, we examine how phosphatases contribute to the regulation of quiescence in mammalian cells across three stages: entry into quiescence, maintenance of the quiescent state, and quiescence exit into the cell cycle. We discuss how phosphatases counteract mitogenic signalling pathways, including MAPK/ERK and PI3K-AKT-mTOR, and maintain low cyclin-dependent kinase (CDK) activity through dephosphorylation of key cell cycle regulators, such as the retinoblastoma family proteins and CDK inhibitors. Finally, we highlight emerging evidence that dynamic regulation of phosphatase activity shapes the transition from quiescence back into proliferation. Understanding how phosphatases regulate the reversible nature of cell cycle arrest is important for understanding how tissues maintain homeostasis and how dysregulation of quiescence contributes to disease, including cancer.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"585-599"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid transport mechanisms in human ABCA family transporters: a structural perspective. 人类ABCA家族转运蛋白的脂质转运机制:结构视角。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250138
Subhrajyoti Dolai, Amer Alam
{"title":"Lipid transport mechanisms in human ABCA family transporters: a structural perspective.","authors":"Subhrajyoti Dolai, Amer Alam","doi":"10.1042/BST20250138","DOIUrl":"10.1042/BST20250138","url":null,"abstract":"<p><p>ATP-binding cassette (ABC) transporters are essential membrane proteins that couple ATP hydrolysis to move diverse substrates across lipid bilayers through large-scale conformational changes. In humans, 48 ABC transporters span seven subfamilies (A-G); within these, the ABCA subfamily mediates cellular lipid handling in contexts ranging from neural function to pulmonary surfactant production, and its dysfunction contributes to human disease from cardiovascular disorders to Alzheimer's. These diverse physiological roles all depend on precise lipid translocation within or across membrane systems, a shared principle that is often underemphasized in broad \"lipid-transporter\" classifications. This review summarizes the structural landscape of the ABCA family and re-examines the mechanistic insights that have emerged. We compare and contrast transport models derived from detergent-solubilized and lipid-embedded structures, with particular emphasis on lipid-embedded ABCA7, which supports a membrane-integrated mechanism in which the bilayer itself contributes to the transport pathway. We highlight shared rigid-body transitions, outline open questions surrounding transport directionality and protein-lipid coupling, and suggest that future models should treat the membrane not merely as a passive scaffold but as an integral component of the transport mechanism, while recognizing that membrane-integrated behavior is currently established structurally only for ABCA7 and remains a working hypothesis for other family members.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"477-488"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Membrane protein structure and dynamics probed by MicroED. 膜蛋白结构与动力学的MicroED探测。
IF 4.4 3区 生物学
Biochemical Society transactions Pub Date : 2026-05-27 DOI: 10.1042/BST20250098
Orel Paz, Tamir Gonen
{"title":"Membrane protein structure and dynamics probed by MicroED.","authors":"Orel Paz, Tamir Gonen","doi":"10.1042/BST20250098","DOIUrl":"10.1042/BST20250098","url":null,"abstract":"<p><p>Membrane proteins are essential to cellular signaling, transport, and homeostasis, yet their amphipathic nature, dependence on lipids or detergents, and typically difficult expression and purification make them difficult targets for structural methods such as X-ray crystallography. Moreover, most membrane proteins in the human proteome are too small for investigation by single-particle electron cryomicroscopy methods. Microcrystal Electron Diffraction (MicroED) has emerged as a powerful method for overcoming these barriers, allowing structure determination from nanocrystals of membrane proteins embedded in the near-native environment of the lipid membrane. In the present review, we discuss how recent improvements in MicroED, such as focused ion-beam milling and high-throughput data collection approaches, facilitate structure determination and investigation of protein dynamics. We focus on applications involving junction-forming proteins, G protein-coupled receptors, and ion channels, where MicroED has revealed physiologically relevant assemblies, lipid interactions, and transient functional states that were not attainable by other structural biology methods.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 5","pages":"489-500"},"PeriodicalIF":4.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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