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Current opinion in structural biology最新文献

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Biochemistry and genetics are coming together to improve our understanding of genotype to phenotype relationships 生物化学和遗传学正在结合在一起，以提高我们对基因型与表型关系的理解。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-11-12 DOI: 10.1016/j.sbi.2024.102952
Judith Notbohm , Tina Perica
{"title":"Biochemistry and genetics are coming together to improve our understanding of genotype to phenotype relationships","authors":"Judith Notbohm ,&nbsp;Tina Perica","doi":"10.1016/j.sbi.2024.102952","DOIUrl":"10.1016/j.sbi.2024.102952","url":null,"abstract":"<div><div>Since genome sequencing became accessible, determining how specific differences in genotypes lead to complex phenotypes such as disease has become one of the key goals in biomedicine. Predicting effects of sequence variants on cellular or organismal phenotype faces several challenges. First, variants simultaneously affect multiple protein properties and predicting their combined effect is complex. Second, effects of changes in a single protein propagate through the cellular network, which we only partially understand. In this review, we emphasize the importance of both biochemistry and genetics in addressing these challenges. Moreover, we highlight work that blurs the distinction between biochemistry and genetics fields to provide new insights into the genotype-to-phenotype relationships.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102952"},"PeriodicalIF":6.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Deep learning for intrinsically disordered proteins: From improved predictions to deciphering conformational ensembles 内在无序蛋白质的深度学习：从改进预测到解密构象组合。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-11-12 DOI: 10.1016/j.sbi.2024.102950
Gábor Erdős, Zsuzsanna Dosztányi
{"title":"Deep learning for intrinsically disordered proteins: From improved predictions to deciphering conformational ensembles","authors":"Gábor Erdős,&nbsp;Zsuzsanna Dosztányi","doi":"10.1016/j.sbi.2024.102950","DOIUrl":"10.1016/j.sbi.2024.102950","url":null,"abstract":"<div><div>Intrinsically disordered proteins (IDPs) lack a stable three-dimensional structure under physiological conditions, challenging traditional structure-based prediction methods. This review explores how modern deep learning approaches, which have revolutionized structure prediction for globular proteins, have impacted protein disorder predictions. We highlight the role of community-driven efforts in curating data and assessing state-of-the-art, which have been crucial in advancing the field. We also review state-of-the-art methods utilizing deep learning techniques, highlighting innovative approaches. We also address advancements in characterizing protein conformational ensembles directly from sequence data using novel machine learning methods.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102950"},"PeriodicalIF":6.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Short circuit: Transcription factor addiction as a growing vulnerability in cancer 短路：转录因子成瘾是癌症中一个日益严重的弱点。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-11-12 DOI: 10.1016/j.sbi.2024.102948
Molly Davies, Maeve Boyce, Eric Conway
{"title":"Short circuit: Transcription factor addiction as a growing vulnerability in cancer","authors":"Molly Davies,&nbsp;Maeve Boyce,&nbsp;Eric Conway","doi":"10.1016/j.sbi.2024.102948","DOIUrl":"10.1016/j.sbi.2024.102948","url":null,"abstract":"<div><div>Core regulatory circuitry refers to the network of lineage-specific transcription factors regulating expression of both their own coding genes, and that of other transcription factors. Such autoregulatory feedback loops coordinate the transcriptome and epigenome during development and cell fate decisions. This circuitry is hijacked during oncogenesis resulting in cancer cell fate being maintained by lineage-specific transcription factors. Major advances in functional genomics and chemical biology are paving the way for a new generation of cancer therapeutics aimed at disrupting this circuitry through both direct and indirect means. Here we review these critical advances in mechanistic understanding of transcription factor addiction in cancer and how the advent of proteolysis targeting chimeras and CRISPR screen assays are leading the way for a new paradigm in targeted cancer treatments.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102948"},"PeriodicalIF":6.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Conformational penalties: New insights into nucleic acid recognition 构象惩罚：核酸识别的新见解。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-11-09 DOI: 10.1016/j.sbi.2024.102949
Ainan Geng , Rohit Roy , Hashim M. Al-Hashimi
{"title":"Conformational penalties: New insights into nucleic acid recognition","authors":"Ainan Geng ,&nbsp;Rohit Roy ,&nbsp;Hashim M. Al-Hashimi","doi":"10.1016/j.sbi.2024.102949","DOIUrl":"10.1016/j.sbi.2024.102949","url":null,"abstract":"<div><div>The energy cost accompanying changes in the structures of nucleic acids when they bind partner molecules is a significant but underappreciated thermodynamic contribution to binding affinity and specificity. This review highlights recent advances in measuring conformational penalties and determining their contribution to the recognition, folding, and regulatory activities of nucleic acids. Notable progress includes methods for measuring and structurally characterizing lowly populated conformational states, obtaining ensemble information in high throughput, for large macromolecular assemblies, and in complex cellular environments. Additionally, quantitative and predictive thermodynamic models have been developed that relate conformational penalties to nucleic acid-protein association and cellular activity. These studies underscore the crucial role of conformational penalties in nucleic acid recognition.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102949"},"PeriodicalIF":6.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 mechano-chemistry of a viral genome packaging motor 病毒基因组包装马达的机械化学原理
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-11-04 DOI: 10.1016/j.sbi.2024.102945
Joshua Pajak , Nikolai S. Prokhorov , Paul J. Jardine , Marc C. Morais
{"title":"The mechano-chemistry of a viral genome packaging motor","authors":"Joshua Pajak ,&nbsp;Nikolai S. Prokhorov ,&nbsp;Paul J. Jardine ,&nbsp;Marc C. Morais","doi":"10.1016/j.sbi.2024.102945","DOIUrl":"10.1016/j.sbi.2024.102945","url":null,"abstract":"<div><div>Double-stranded DNA viruses actively package their genomes into pre-assembled protein capsids using energy derived from virus-encoded ASCE ATPase ring motors. Single molecule experiments in the aughts and early 2010s demonstrated that these motors are some of the most powerful molecular motors in nature, and that the activities of individual subunits around the ATPase ring motor are highly coordinated to ensure efficient genome encapsidation. While these studies provided a comprehensive kinetic scheme describing the events that occur during packaging, the physical basis of force generation and subunit coordination remained elusive. This article reviews recent structural and computational results that have begun to illuminate the molecular basis of force generation and DNA translocation in these powerful molecular motors.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102945"},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Characterizing protein-protein interactions with thermal proteome profiling 利用热蛋白质组图谱鉴定蛋白质与蛋白质之间的相互作用
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-30 DOI: 10.1016/j.sbi.2024.102946
Brian C. Searle
{"title":"Characterizing protein-protein interactions with thermal proteome profiling","authors":"Brian C. Searle","doi":"10.1016/j.sbi.2024.102946","DOIUrl":"10.1016/j.sbi.2024.102946","url":null,"abstract":"<div><div>Thermal proteome profiling (TPP) is an innovative technique that uses the principle of protein thermal stability to identify potential protein interaction partners. Employing quantitative mass spectrometry, TPP measures protein stability across the proteome, offering a comprehensive snapshot of protein interactions in a single experiment. When studying protein-protein interactions (PPI), TPP leverages changes in apparent protein melting temperatures to identify transient and weak interactions that most traditional PPI detection methodologies struggle to measure. This review discusses current TPP methodologies, the challenges of interpreting the resulting complex datasets, and opportunities to deepen and improve PPI networks. By advancing our grasp of intricate protein interactions, TPP promises to illuminate the molecular basis of diseases and drive the discovery of novel therapeutic targets.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102946"},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Retraction notice to “Liquid-EM goes viral – visualizing structure and dynamics” [Curr Opin Struct Biol 75 (August 2022) 102426] 液体电子显微镜（Liquid-EM）病毒式传播--结构与动力学可视化》撤稿通知 [Curr Opin Struct Biol 75 (August 2022) 102426]
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-28 DOI: 10.1016/j.sbi.2024.102947
Deborah F. Kelly , Liza-Anastasia DiCecco , G.M. Jonaid , William J. Dearnaley , Michael S. Spilman , Jennifer L. Gray , Madeline J. Dressel-Dukes
{"title":"Retraction notice to “Liquid-EM goes viral – visualizing structure and dynamics” [Curr Opin Struct Biol 75 (August 2022) 102426]","authors":"Deborah F. Kelly ,&nbsp;Liza-Anastasia DiCecco ,&nbsp;G.M. Jonaid ,&nbsp;William J. Dearnaley ,&nbsp;Michael S. Spilman ,&nbsp;Jennifer L. Gray ,&nbsp;Madeline J. Dressel-Dukes","doi":"10.1016/j.sbi.2024.102947","DOIUrl":"10.1016/j.sbi.2024.102947","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102947"},"PeriodicalIF":6.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Non-canonical amino acids for site-directed spin labeling of membrane proteins 用于膜蛋白定点自旋标记的非典型氨基酸。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-24 DOI: 10.1016/j.sbi.2024.102936
Kaitlyn Ledwitch , Georg Künze , Elleansar Okwei , Davide Sala , Jens Meiler
{"title":"Non-canonical amino acids for site-directed spin labeling of membrane proteins","authors":"Kaitlyn Ledwitch ,&nbsp;Georg Künze ,&nbsp;Elleansar Okwei ,&nbsp;Davide Sala ,&nbsp;Jens Meiler","doi":"10.1016/j.sbi.2024.102936","DOIUrl":"10.1016/j.sbi.2024.102936","url":null,"abstract":"<div><div>Membrane proteins remain challenging targets for conventional structural biology techniques because they need to reside within complex hydrophobic lipid environments to maintain proper structure and function. Magnetic resonance combined with site-directed spin labeling is an alternative method that provides atomic-level structural and dynamical information from effects introduced by an electron- or nuclear-based spin label. With the advent of bioorthogonal click chemistries and genetically engineered non-canonical amino acids (ncAAs), options for linking spin probes to biomolecules have substantially broadened outside the conventional cysteine-based labeling scheme. Here, we highlight current strategies to spin-label membrane proteins through ncAAs for nuclear and electron paramagnetic resonance applications. Such advances are critical for developing bioorthogonal spin labeling schemes to achieve in-cell labeling and in-cell measurements of membrane protein conformational dynamics.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102936"},"PeriodicalIF":6.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Empowering the molecular ruler techniques with unnatural base pair system to explore conformational dynamics of flaviviral RNAs 利用非天然碱基配对系统增强分子尺技术，探索黄病毒 RNA 的构象动力学。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-22 DOI: 10.1016/j.sbi.2024.102944
Jie Zhang , Xianyang Fang
{"title":"Empowering the molecular ruler techniques with unnatural base pair system to explore conformational dynamics of flaviviral RNAs","authors":"Jie Zhang ,&nbsp;Xianyang Fang","doi":"10.1016/j.sbi.2024.102944","DOIUrl":"10.1016/j.sbi.2024.102944","url":null,"abstract":"<div><div>RNA's inherent flexibility and dynamics pose great challenges to characterize its structure and dynamics using conventional techniques including X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy. Three complementary molecular ruler techniques, the electron paramagnetic resonance (EPR) spectroscopy, X-ray scattering interferometry (XSI) and Förster resonance energy transfer (FRET) which measure intramolecular and intermolecular pair-wise distance distributions in the nanometer range in a solution, have become increasingly popular and been widely used to explore RNA structure and dynamics. The prerequisites for successful application of such techniques are to achieve site-specific labeling of RNAs with spin labels, fluorescent tags, or gold nanoparticles, respectively, which are however, challenging, especially to large RNAs (generally &gt;200 nts). Here, we briefly review the basics of these molecular rulers, how the NaM-TPT3 unnatural base pair system empower them, and their applications to explore conformational dynamics of large RNAs, especially in the context of flavivirus RNA genome.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102944"},"PeriodicalIF":6.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Editorial overview: Cryo-electron microscopy 编辑综述：冷冻电镜。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-19 DOI: 10.1016/j.sbi.2024.102937
Pilar Cossio, Edward Egelman
{"title":"Editorial overview: Cryo-electron microscopy","authors":"Pilar Cossio,&nbsp;Edward Egelman","doi":"10.1016/j.sbi.2024.102937","DOIUrl":"10.1016/j.sbi.2024.102937","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102937"},"PeriodicalIF":6.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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