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Progress toward a comprehensive brain protein interactome. 建立全面的大脑蛋白质相互作用组的进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-12 DOI: 10.1042/BST20241135
Vy Dang, Brittney Voigt, Edward M Marcotte
{"title":"Progress toward a comprehensive brain protein interactome.","authors":"Vy Dang, Brittney Voigt, Edward M Marcotte","doi":"10.1042/BST20241135","DOIUrl":"https://doi.org/10.1042/BST20241135","url":null,"abstract":"<p><p>Protein-protein interactions (PPIs) in the brain play critical roles across all aspects of the central nervous system, from synaptic transmission, glial development, myelination, to cell-to-cell communication, and more. Understanding these interactions is crucial for deciphering neurological mechanisms and the underlying biochemical machinery affected in neurological disorders. Recently, advances in proteomics techniques have significantly enhanced our ability to study interactions among the proteins expressed in the brain. Here, we review some of the high-throughput studies characterizing brain PPIs, using affinity purification, proximity labeling, co-fractionation, and chemical cross-linking mass spectrometry methods, as well as yeast two-hybrid assays. We present the current state of the field, discuss challenges, and highlight promising future directions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-10 DOI: 10.1042/BST20241633
Lauryn Buckley-Benbow, Alessandro Agnarelli, Roberto Bellelli
{"title":"'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.","authors":"Lauryn Buckley-Benbow, Alessandro Agnarelli, Roberto Bellelli","doi":"10.1042/BST20241633","DOIUrl":"https://doi.org/10.1042/BST20241633","url":null,"abstract":"<p><p>The introduction of poly-ADP ribose polymerase (PARP) inhibitors (PARPi) has completely changed the treatment landscape of breast cancer susceptibility 1-2 (BRCA1-BRCA2)-mutant cancers and generated a new avenue of research in the fields of DNA damage response and cancer therapy. Despite this, primary and secondary resistances to PARPi have become a challenge in the clinic, and novel therapies are urgently needed to address this problem. After two decades of research, a unifying model explaining sensitivity of cancer cells to PARPi is still missing. Here, we review the current knowledge in the field and the increasing evidence pointing to a crucial role for replicative gaps in mediating sensitization to PARPi in BRCA-mutant and 'wild-type' cancer cells. Finally, we discuss the challenges to be addressed to further improve the utilization of PARPi and tackle the emergence of resistance in the clinical context.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Conformational dynamics of the nuclear pore complex central channel.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20240507
Yu Chen, Guoli Zhou, Miao Yu
{"title":"Conformational dynamics of the nuclear pore complex central channel.","authors":"Yu Chen, Guoli Zhou, Miao Yu","doi":"10.1042/BST20240507","DOIUrl":"https://doi.org/10.1042/BST20240507","url":null,"abstract":"<p><p>The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At the heart of the NPC's function are intrinsically disordered phenylalanineglycine-rich nucleoporins (FG-Nups), which form a dynamic permeability barrier within the central channel. This disordered nature facilitates efficient nucleocytoplasmic transport but also poses significant challenges to its characterization, especially within the nano-confined environment of the NPC. Recent advances in experimental techniques, such as cryo-electron microscopy, atomic force microscopy, fluorescence microscopy, and nuclear magnetic resonance, along with computational modeling, have illuminated the conformational flexibility of FG-Nups, which underpins their functional versatility. This review synthesizes these advancements, emphasizing how disruptions in FG-Nup behavior-caused by mutations or pathological interactions-contribute to diseases such as neurodegenerative disorders, aging-related decline, and viral infections. Despite progress, challenges persist in deciphering FG-Nup dynamics within the crowded and complex cellular environment, especially under pathological conditions. Addressing these gaps is critical for advancing therapeutic strategies targeting NPC dysfunction in disease progression.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polymer models of chromatin organization in virally infected cells.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20240598
Andrea Fontana, Fabrizio Tafuri, Alex Abraham, Simona Bianco, Andrea Esposito, Mattia Conte, Francesca Vercellone, Florinda Di Pierno, Sougata Guha, Ciro Di Carluccio, Andrea M Chiariello
{"title":"Polymer models of chromatin organization in virally infected cells.","authors":"Andrea Fontana, Fabrizio Tafuri, Alex Abraham, Simona Bianco, Andrea Esposito, Mattia Conte, Francesca Vercellone, Florinda Di Pierno, Sougata Guha, Ciro Di Carluccio, Andrea M Chiariello","doi":"10.1042/BST20240598","DOIUrl":"10.1042/BST20240598","url":null,"abstract":"<p><p>Genome architecture is closely tied to essential biological functions, yet a complete understanding of the mechanisms governing DNA folding remains a significant challenge. Theoretical models based on polymer physics have been applied to decipher the complexity of chromatin architecture and uncover the physical processes shaping its structure. Importantly, recent findings suggest that certain viruses can alter the 3D organization of the host genome. In this review, we highlight recent advances in the development of polymer models used to study how chromatin 3D structure within a cell re-organizes following viral infection, with a particular emphasis on the SARS-CoV-2 virus, capable of altering genome organization of the host cell at different scales, including A/B compartments, TADs and gene-enhancer regulatory contacts.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20241419
Mohammed Al-Seragi, Yilun Chen, Franck Duong van Hoa
{"title":"Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.","authors":"Mohammed Al-Seragi, Yilun Chen, Franck Duong van Hoa","doi":"10.1042/BST20241419","DOIUrl":"https://doi.org/10.1042/BST20241419","url":null,"abstract":"<p><p>NANOBODIES® (Nbs) have emerged as valuable tools across therapeutic, diagnostic, and industrial applications owing to their small size and consequent ability to bind unique epitopes inaccessible to conventional antibodies. While Nbs retrieved from immune libraries normally possess sufficient affinity and specificity for their cognate antigens in the practical use case, their multimerization will often increase functional affinity via avidity effects. Therefore, to rescue binding affinity and broaden targeting specificities, recent efforts have focused on conjugating multiple Nb clones - of identical or unique antigen cognates - together. In vivo and in vitro approaches, including flexible linkers, antibody domains, self-assembling coiled coils, chemical conjugation, and self-clustering hydrophobic sequences, have been employed to produce multivalent and multispecific Nb constructs. Examples of successful Nb multimerization are diverse, ranging from immunoassaying reagents to virus-neutralizing moieties. This review aims to recapitulate the in vivo and in vitro modalities to produce multivalent and multispecific Nbs while highlighting the applications, advantages, and drawbacks tied to each method.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advancing structure modeling from cryo-EM maps with deep learning.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-07 DOI: 10.1042/BST20240784
Shu Li, Genki Terashi, Zicong Zhang, Daisuke Kihara
{"title":"Advancing structure modeling from cryo-EM maps with deep learning.","authors":"Shu Li, Genki Terashi, Zicong Zhang, Daisuke Kihara","doi":"10.1042/BST20240784","DOIUrl":"https://doi.org/10.1042/BST20240784","url":null,"abstract":"<p><p>Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of biomolecular structures that are challenging to resolve using conventional methods. Interpreting a cryo-EM map requires accurate modeling of the structures of underlying biomolecules. Here, we concisely discuss the evolution and current state of automatic structure modeling from cryo-EM density maps. We classify modeling methods into two categories: de novo modeling methods from high-resolution maps (better than 5 Å) and methods that model by fitting individual structures of component proteins to maps at lower resolution (worse than 5 Å). Special attention is given to the role of deep learning in the modeling process, highlighting how AI-driven approaches are transformative in cryo-EM structure modeling. We conclude by discussing future directions in the field.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Small RNA-mediated suppression of sex chromosome meiotic conflicts during Drosophila male gametogenesis.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240344
Jeffrey Vedanayagam
{"title":"Small RNA-mediated suppression of sex chromosome meiotic conflicts during Drosophila male gametogenesis.","authors":"Jeffrey Vedanayagam","doi":"10.1042/BST20240344","DOIUrl":"10.1042/BST20240344","url":null,"abstract":"<p><p>Meiosis is an evolutionarily conserved process in eukaryotes that ensures equal segregation of alleles and chromosomes during reproduction. Although parity in allelic transmission is the norm, selfish genes such as meiotic drivers can violate Mendel's first law of segregation. Sex chromosome drive is a form of meiotic drive that leads to unequal segregation of sex chromosomes, resulting in sex-ratio distortion and/or sterility in the offspring. Adverse fitness effects due to sex chromosome drive trigger the evolution of suppressors to restore Mendelian segregation. However, the molecular mechanisms by which suppressors emerge and counteract meiotic drive genes remain unclear. Recent studies from Drosophila have shed light on the critical roles of small RNA-mediated post-transcriptional silencing in mitigating sex chromosome meiotic conflicts. This review highlights the recruitment of two distinct small RNA pathways to combat intragenomic conflicts during male gametogenesis and seeks to reveal the impact of molecular arms races between meiotic drivers and their suppressors in shaping genome and sex chromosome evolution.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of transcription bodies in gene expression: what embryos teach us.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240599
Martino Ugolini, Nadine L Vastenhouw
{"title":"The role of transcription bodies in gene expression: what embryos teach us.","authors":"Martino Ugolini, Nadine L Vastenhouw","doi":"10.1042/BST20240599","DOIUrl":"https://doi.org/10.1042/BST20240599","url":null,"abstract":"<p><p>Transcription does not occur diffusely throughout the nucleus but is concentrated in specific areas. Areas of accumulated transcriptional machinery have been called clusters, hubs, or condensates, while transcriptionally active areas have been referred to as transcription factories or transcription bodies. Despite the widespread occurrence of transcription bodies, it has been difficult to study their assembly, function, and effect on gene expression. This review highlights the advantages of developmental model systems such as zebrafish and fruit fly embryos, in addressing these questions. We focus on three important discoveries that were made in embryos. (i) It had previously been suggested that, in transcription bodies, the different steps of the transcription process are organized in space. We explore how work in embryos has revealed that they can also be organized in time. In this case, transcription bodies mature from transcription factor clusters to elongating transcription bodies. This type of organization has important implications for transcription body function. (ii) The relevance of clustering for in vivo gene regulation has benefited greatly from studies in embryos. We discuss examples in which transcription bodies regulate developmental gene expression by compensating for low transcription factor concentrations and low-affinity enhancers. Finally, (iii) while accumulations of transcriptional machinery can facilitate transcription locally, work in embryos showed that transcription bodies can also sequester the transcriptional machinery, modulating the availability for activity at other sites. In brief, the reviewed literature highlights the properties of developmental model organisms that make them powerful systems for uncovering the form and function of transcription bodies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240422
Zhou Chen, Daniel L Minor
{"title":"Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.","authors":"Zhou Chen, Daniel L Minor","doi":"10.1042/BST20240422","DOIUrl":"https://doi.org/10.1042/BST20240422","url":null,"abstract":"<p><p>Ion channels are multicomponent complexes (termed here as\"electrosomes\") that conduct the bioelectrical signals required for life. It has been appreciated for decades that assembly is critical for proper channel function, but knowledge of the factors that undergird this important process has been lacking. Although there are now exemplar structures of representatives of most major ion channel classes, there has been no direct structural information to inform how these complicated, multipart complexes are put together or whether they interact with chaperone proteins that aid in their assembly. Recent structural characterization of a complex of the endoplasmic membrane protein complex (EMC) chaperone and a voltage-gated calcium channel (CaV) assembly intermediate comprising the pore-forming CaVα1 and cytoplasmic CaVβ subunits offers the first structural view into the assembly of a member of the largest ion channel class, the voltagegated ion channel (VGIC) superfamily. The structure shows how the EMC remodels the CaVα1/CaVβ complex through a set of rigid body movements for handoff to the extracellular CaVα2δ subunit to complete channel assembly in a process that involves intersubunit coordination of a divalent cation and ordering of CaVα1 elements. These findings set a new framework for deciphering the structural underpinnings of ion channel biogenesis that has implications for understanding channel function, how drugs and disease mutations act, and for investigating how other membrane proteins may engage the ubiquitous EMC chaperone.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Same same but different? How blood and lymphatic vessels induce cell contact inhibition.
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240573
Claudia Carlantoni, Leon M H Liekfeld, Manu Beerens, Maike Frye
{"title":"Same same but different? How blood and lymphatic vessels induce cell contact inhibition.","authors":"Claudia Carlantoni, Leon M H Liekfeld, Manu Beerens, Maike Frye","doi":"10.1042/BST20240573","DOIUrl":"https://doi.org/10.1042/BST20240573","url":null,"abstract":"<p><p>Endothelial cells (ECs) migrate, sprout, and proliferate in response to (lymph)angiogenic mitogens, such as vascular endothelial growth factors. When ECs reach high confluency and encounter spatial confinement, they establish mature cell-cell junctions, reduce proliferation, and enter a quiescent state through a process known as contact inhibition. However, EC quiescence is modulated not only by spatial confinement but also by other mechano-environmental factors, including blood or lymph flow and extracellular matrix properties. Changes in physical forces and intracellular signaling can disrupt contact inhibition, resulting in aberrant proliferation and vascular dysfunction. Therefore, it is critical to understand the mechanisms by which endothelial cells regulate contact inhibition. While contact inhibition has been well studied in blood endothelial cells (BECs), its regulation in lymphatic endothelial cells (LECs) remains largely unexplored. Here, we review the current knowledge on extrinsic stimuli and intrinsic molecular pathways that govern endothelial contact inhibition and highlight nuanced differences between BECs and LECs. Furthermore, we provide perspectives for future research on lymphatic contact inhibition. A deeper understanding of the BEC and LEC-specific pathways underlying contact inhibition may enable targeted modulation of this process in blood or lymphatic vessels with relevance to lymphatic or blood vascular-specific disorders.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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