Biochemical Society transactions最新文献

Mimetics of in-cell and subcellular crowding and solvation for protein folding. 模拟细胞内和亚细胞拥挤和蛋白质折叠的溶剂化。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-30 DOI: 10.1042/BST20250108

Edward Knab, Ume Tahir, Caitlin M Davis

{"title":"Mimetics of in-cell and subcellular crowding and solvation for protein folding.","authors":"Edward Knab, Ume Tahir, Caitlin M Davis","doi":"10.1042/BST20250108","DOIUrl":"10.1042/BST20250108","url":null,"abstract":"Historically, fundamental principles of protein folding were extracted from dilute in vitro experiments that disregarded the complexity of the cell interior. It is now well-established that the cellular environment modulates protein behaviors. Discrepancies between protein properties measured in vitro and in-cell can be disentangled using mimetics that are designed to reproduce cellular interactions in vitro, steric crowding interactions and non-steric sticking interactions. Here, we review recent advances in the development and application of cellular mimetics of in-cell protein folding, with a focus on replicating diverse cell types and cellular compartments. Steric crowding interactions are typically mimicked using inert polymers; coupling these with giant unilamellar vesicles or phase separation allows for the creation of a cell- or organelle-like environment. Mimetics of non-steric chemical interactions must incorporate features of the chemical environment being mimicked. These range from buffers containing physiological concentrations of salt and small molecules to dilute lysates derived from the relevant cell type and/or organelle. Such mimetics of steric and non-steric interactions have greatly aided our understanding of in-cell protein folding. Mimetics can further approach biological accuracy through mixtures that simultaneously account for steric and non-steric interactions. Mimetic mixtures are important because they provide a convenient and cost-effective means to predict protein behavior in diverse cellular environments, which may benefit high-throughput applications, such as screening therapeutic candidates or training machine learning-based in-cell protein structure prediction models.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"413-425"},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760806","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

How intrinsically disordered regions shape the function of CREB-binding protein. 内在无序区域如何塑造creb结合蛋白的功能。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-30 DOI: 10.1042/BST20250492

Grace Gilbert, Daniel A Bose

{"title":"How intrinsically disordered regions shape the function of CREB-binding protein.","authors":"Grace Gilbert, Daniel A Bose","doi":"10.1042/BST20250492","DOIUrl":"10.1042/BST20250492","url":null,"abstract":"CREB-binding protein (CBP) is a histone acetyltransferase and transcriptional co-activator that operates across the genome at cis-regulatory elements (CREs) to regulate gene expression. Comprising the majority of the protein, CBP has intrinsically disordered regions (IDRs) that separate its folded domains. Whilst previously regarded as passive linkers, active roles for these IDRs within CBP are beginning to be uncovered. Firstly, the flexibility afforded by these regions and the presence of binding motifs within them establish CBP as an interaction specialist that is able to interact with many binding partners at diverse CREs. In addition, the IDRs of CBP allow it to undergo liquid-liquid phase separation, forming condensates with emerging roles in transcription. Finally, an IDR within CBP performs an autoregulatory function that makes histone acetyltransferase activity sensitive to changing conditions within the cell. To build a comprehensive understanding of CBP function going forwards, it will be necessary to consider the contributions of the IDRs in addition to the structured domains of CBP and how these are integrated for the regulation of this key transcriptional protein.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"403-411"},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760790","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

The amplification of α-synuclein amyloid fibrils. α-突触核蛋白淀粉样原纤维扩增。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-30 DOI: 10.1042/BST20250489

Alexander K Buell

{"title":"The amplification of α-synuclein amyloid fibrils.","authors":"Alexander K Buell","doi":"10.1042/BST20250489","DOIUrl":"10.1042/BST20250489","url":null,"abstract":"Amyloid fibrils formed by α-synuclein are a hallmark of a range of neurodegenerative diseases, notably Parkinson's disease, multiple system atrophy (MSA), and dementia with Lewy bodies, collectively known as synucleinopathies. Recent years have seen an increasing understanding of the structural architecture and diversity of α-synuclein amyloid fibrils. Furthermore, our mechanistic understanding of the formation of these structures has also experienced significant progress. Here, I provide a concise overview of the current state of knowledge of how α-synuclein amyloid fibrils can be amplified, i.e., increase in number. The main emphasis is thereby on the process of secondary nucleation, i.e., the generation of new amyloid fibrils catalyzed by existing fibrils. A detailed understanding of fibril amplification is relevant in the context of the spread of pathology in the central nervous system of synucleinopathy patients. In addition, it can also be exploited in the framework of diagnostic approaches collectively known as seed amplification assays (SAAs). In such assays, the minute quantities of α-synuclein fibrils present in biological fluids are amplified and possibly quantified for disease diagnostics.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"427-435"},"PeriodicalIF":4.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760757","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

Advances in polarised luminescence approaches to understanding interactions between biomolecules. 偏振发光方法在理解生物分子间相互作用方面的进展。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-29 DOI: 10.1042/BST20253138

Edan Habel, Pinky Vishwakarma, Thomas Huber, Alison Rodger

引用次数: 0

The role of HNF4α in adenocarcinoma. HNF4α在腺癌中的作用。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-29 DOI: 10.1042/BST20253085

Headtlove Essel Dadzie, Eric L Snyder

{"title":"The role of HNF4α in adenocarcinoma.","authors":"Headtlove Essel Dadzie, Eric L Snyder","doi":"10.1042/BST20253085","DOIUrl":"10.1042/BST20253085","url":null,"abstract":"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.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"333-347"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589627","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

The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting. 肿瘤的综合应激反应：肿瘤适应机制和治疗靶向。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-29 DOI: 10.1042/BST20250133

Elias Maldonado, Emily McIsaac, Josie Ursini-Siegel

{"title":"The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.","authors":"Elias Maldonado, Emily McIsaac, Josie Ursini-Siegel","doi":"10.1042/BST20250133","DOIUrl":"10.1042/BST20250133","url":null,"abstract":"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.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"363-374"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760781","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

Glutamine metabolic enzymes: to filament or not to filament? 谷氨酰胺代谢酶：成丝还是不成丝？

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-29 DOI: 10.1042/BST20253136

Raquel A C Machado, Ivan Rosa E Silva, Thaís Fontes-Milz, Yuan Chang-Halabi, Jhon A Vargas, Andre L B Ambrosio, Sandra M G Dias

{"title":"Glutamine metabolic enzymes: to filament or not to filament?","authors":"Raquel A C Machado, Ivan Rosa E Silva, Thaís Fontes-Milz, Yuan Chang-Halabi, Jhon A Vargas, Andre L B Ambrosio, Sandra M G Dias","doi":"10.1042/BST20253136","DOIUrl":"10.1042/BST20253136","url":null,"abstract":"The self-assembly of metabolic enzymes into filaments and other supramolecular structures is well-documented in bacteria and yeast but remains largely unexplored in mammalian cells. Enzyme filamentation is thought to play a crucial role in regulating metabolic networks by modulating enzymatic activity in response to cellular demands. Studies in yeast suggest that filament-forming enzymes are often positioned at key junctions of metabolic pathways, enabling dynamic activation or inactivation during growth or stress and directing metabolic flux accordingly. While this mechanism appears to be broadly conserved across species, the structural and functional characterization of human homologs of filamentous enzymes remains limited. In the present review, we focus on the glutamine metabolic pathway, highlighting enzymes known to form large self-assemblies in cells and examining the few cases where structural insights are available. Finally, we discuss the broader implications of metabolic enzyme filamentation in mammalian cells, underscoring its potential as an emerging area of research.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"375-392"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760754","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

Emerging concepts of reactive oxygen species functions in plants. 活性氧在植物中的作用的新概念。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-04-29 DOI: 10.1042/BST20250107

Christine H Foyer

{"title":"Emerging concepts of reactive oxygen species functions in plants.","authors":"Christine H Foyer","doi":"10.1042/BST20250107","DOIUrl":"10.1042/BST20250107","url":null,"abstract":"Reactive oxygen species (ROS) are ubiquitous signalling molecules that serve to integrate developmental, metabolic and stress signals to shape adaptive outcomes, linking energy metabolism to plant physiology, growth and stress resilience in a changing world. Resolving the factors and mechanisms involved in ROS-mediated control has proved to be far from trivial, not least because ROS are produced by every compartment of plant cells, serving multiple functions with numerous points of reciprocal control between phytohormones and other signalling pathways. While many enzymes produce hydrogen peroxide (H2O2) directly, other ROS sources such as respiratory burst oxidase homologues (RBOH) produce superoxide as a primary product. Key questions remain concerning the respective roles of superoxide and H2O2 in redox regulation of plant growth, development and defence, and how plant cells can differentiate between ROS produced in different cellular compartments. One solution concerns cysteine (Cys) molecular switches, which are specialised protein thiols that operate as highly sensitive ROS sensors in different locations, transducing changes in oxidation status to the nucleus and facilitating functional changes in protein activity, structure, and localisation. In addition, it is likely that the localisation and positions of many redox proteins, such as catalase and RBOH, are not as fixed as initially proposed, allowing plasticity of function in different compartments. This review discusses current concepts in plant ROS biology, highlighting novel aspects that permeate every aspect of plant biology.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 4","pages":"393-402"},"PeriodicalIF":4.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760822","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

Heme oxygenase-like dimetal oxidases and oxygenases. 血红素加氧酶样二金属氧化酶和加氧酶。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-03-25 DOI: 10.1042/BST20253134

Sydney S Skirboll, Anastasia E Ledinina, Thomas M Makris

引用次数: 0

Breaking cellular boundaries: molecular mechanisms of tunneling nanotube formation and fusion. 打破细胞边界：隧道纳米管形成和融合的分子机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-03-25 DOI: 10.1042/BST20250093

Sevan Belian, Chiara Zurzolo

{"title":"Breaking cellular boundaries: molecular mechanisms of tunneling nanotube formation and fusion.","authors":"Sevan Belian, Chiara Zurzolo","doi":"10.1042/BST20250093","DOIUrl":"10.1042/BST20250093","url":null,"abstract":"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.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442421","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