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Advances in the molecular understanding of GPCR-arrestin complexes. 对 GPCR-arrestin复合物的分子认识取得进展。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240170
Ivana Petrovic, Stephan Grzesiek, Polina Isaikina
{"title":"Advances in the molecular understanding of GPCR-arrestin complexes.","authors":"Ivana Petrovic, Stephan Grzesiek, Polina Isaikina","doi":"10.1042/BST20240170","DOIUrl":"10.1042/BST20240170","url":null,"abstract":"<p><p>Arrestins are essential proteins for the regulation of G protein-coupled receptors (GPCRs). They mediate GPCR desensitization after the activated receptor has been phosphorylated by G protein receptor kinases (GRKs). In addition, GPCR-arrestin interactions may trigger signaling pathways that are distinct and independent from G proteins. The non-visual GPCRs encompass hundreds of receptors with varying phosphorylation patterns and amino acid sequences, which are regulated by only two human non-visual arrestin isoforms. This review describes recent findings on GPCR-arrestin complexes, obtained by structural techniques, biophysical, biochemical, and cellular assays. The solved structures of complete GPCR-arrestin complexes are of limited resolution ranging from 3.2 to 4.7 Å and reveal a high variability in the relative receptor-arrestin orientation. In contrast, biophysical and functional data indicate that arrestin recruitment, activation and GPCR-arrestin complex stability depend on the receptor phosphosite sequence patterns and density. At present, there is still a manifest lack of high-resolution structural and dynamical information on the interactions of native GPCRs with both GRKs and arrestins, which could provide a detailed molecular understanding of the genesis of receptor phosphorylation patterns and the specificity GPCR-arrestin interactions. Such insights seem crucial for progress in the rational design of advanced, arrestin-specific therapeutics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2333-2342"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602729","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
Age-dependent regenerative mechanisms in the brain. 大脑中与年龄有关的再生机制。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20230547
Giada Vanacore, Jens Bager Christensen, N Sumru Bayin
{"title":"Age-dependent regenerative mechanisms in the brain.","authors":"Giada Vanacore, Jens Bager Christensen, N Sumru Bayin","doi":"10.1042/BST20230547","DOIUrl":"10.1042/BST20230547","url":null,"abstract":"<p><p>Repairing the adult mammalian brain represents one of the greatest clinical challenges in medicine. Injury to the adult brain often results in substantial loss of neural tissue and permanent functional impairment. In contrast with the adult, during development, the mammalian brain exhibits a remarkable capacity to replace lost cells. A plethora of cell-intrinsic and extrinsic factors regulate the age-dependent loss of regenerative potential in the brain. As the developmental window closes, neural stem cells undergo epigenetic changes, limiting their proliferation and differentiation capacities, whereas, changes in the brain microenvironment pose additional challenges opposing regeneration, including inflammation and gliosis. Therefore, studying the regenerative mechanisms during development and identifying what impairs them with age may provide key insights into how to stimulate regeneration in the brain. Here, we will discuss how the mammalian brain engages regenerative mechanisms upon injury or neuron loss. Moreover, we will describe the age-dependent changes that affect these processes. We will conclude by discussing potential therapeutic approaches to overcome the age-dependent regenerative decline and stimulate regeneration.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2243-2252"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709187","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 role of protein O-GlcNAcylation in diabetic cardiomyopathy. 蛋白质 O-GlcNAcylation 在糖尿病心肌病中的作用。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240262
John C Chatham, Adam R Wende
{"title":"The role of protein O-GlcNAcylation in diabetic cardiomyopathy.","authors":"John C Chatham, Adam R Wende","doi":"10.1042/BST20240262","DOIUrl":"10.1042/BST20240262","url":null,"abstract":"<p><p>It is well established that diabetes markedly increases the risk of multiple types of heart disease including heart failure. However, despite substantial improvements in the treatment of heart failure in recent decades the relative increased risk associated with diabetes remains unchanged. There is increasing appreciation of the importance of the post translational modification by O-linked-N-acetylglucosamine (O-GlcNAc) of serine and threonine residues on proteins in regulating cardiomyocyte function and mediating stress responses. In response to diabetes there is a sustained increase in cardiac O-GlcNAc levels, which has been attributed to many of the adverse effects of diabetes on the heart. Here we provide an overview of potential mechanisms by which increased cardiac O-GlcNAcylation contributes to the adverse effects on the heart and highlight some of the key gaps in our knowledge.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2343-2358"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724382","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
Tools and techniques for quantitative glycoproteomic analysis. 定量糖蛋白组学分析的工具和技术。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240257
Siyuan Kong, Wei Zhang, Weiqian Cao
{"title":"Tools and techniques for quantitative glycoproteomic analysis.","authors":"Siyuan Kong, Wei Zhang, Weiqian Cao","doi":"10.1042/BST20240257","DOIUrl":"10.1042/BST20240257","url":null,"abstract":"<p><p>Recent advances in mass spectrometry (MS)-based methods have significantly expanded the capabilities for quantitative glycoproteomics, enabling highly sensitive and accurate quantitation of glycosylation at intact glycopeptide level. These developments have provided valuable insights into the roles of glycoproteins in various biological processes and diseases. In this short review, we summarize pertinent studies on quantitative techniques and tools for site-specific glycoproteomic analysis published over the past decade. We also highlight state-of-the-art MS-based software that facilitate multi-dimension quantification of the glycoproteome, targeted quantification of specific glycopeptides, and the analysis of glycopeptide isomers. Additionally, we discuss the potential applications of these technologies in clinical biomarker discovery and the functional characterization of glycoproteins in health and disease. The review concludes with a discussion of current challenges and future perspectives in the field, emphasizing the need for more precise, high-throughput and efficient methods to further advance quantitative glycoproteomics and its applications.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2439-2453"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799466","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
Linking glycosphingolipid metabolism to disease-related changes in the plasma membrane proteome. 鞘糖脂代谢与质膜蛋白质组疾病相关变化的联系
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240315
Holly Monkhouse, Janet E Deane
{"title":"Linking glycosphingolipid metabolism to disease-related changes in the plasma membrane proteome.","authors":"Holly Monkhouse, Janet E Deane","doi":"10.1042/BST20240315","DOIUrl":"10.1042/BST20240315","url":null,"abstract":"<p><p>Glycosphingolipids (GSLs) are vital components of the plasma membrane (PM), where they play crucial roles in cell function. GSLs form specialised membrane microdomains that organise lipids and proteins into functional platforms for cell adhesion and signalling. GSLs can also influence the function of membrane proteins and receptors, via direct protein-lipid interactions thereby affecting cell differentiation, proliferation, and apoptosis. Research into GSL-related diseases has primarily focussed on lysosomal storage disorders, where defective enzymes lead to the accumulation of GSLs within lysosomes, causing cellular dysfunction and disease. However, recent studies are uncovering the broader cellular impact of GSL imbalances including on a range of organelles and cellular compartments such as the mitochondria, endoplasmic reticulum and PM. In this review we describe the mechanisms by which GSL imbalances can influence the PM protein composition and explore examples of the changes that have been observed in the PM proteome upon GSL metabolic disruption. Identifying and understanding these changes to the PM protein composition will enable a more complete understanding of lysosomal storage diseases and provide new insights into the pathogenesis of other GSL-related diseases, including cancer and neurodegenerative disorders.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2477-2486"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783962","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
Adding a twist to the loops: the role of DNA superhelicity in the organization of chromosomes by SMC protein complexes. 在环上增加一个扭曲:DNA超螺旋在SMC蛋白复合体染色体组织中的作用。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240650
Antonio Valdés, Christian H Haering
{"title":"Adding a twist to the loops: the role of DNA superhelicity in the organization of chromosomes by SMC protein complexes.","authors":"Antonio Valdés, Christian H Haering","doi":"10.1042/BST20240650","DOIUrl":"10.1042/BST20240650","url":null,"abstract":"<p><p>Structural maintenance of chromosomes (SMC) protein complexes, including cohesin, condensin, and the Smc5/6 complex, are integral to various processes in chromosome biology. Despite their distinct roles, these complexes share two key properties: the ability to extrude DNA into large loop structures and the capacity to alter the superhelicity of the DNA double helix. In this review, we explore the influence of eukaryotic SMC complexes on DNA topology, debate its potential physiological function, and discuss new structural insights that may explain how these complexes mediate changes in DNA topology.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"52 6","pages":"2487-2497"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862913","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
Insights into mechanisms of ubiquitin ADP-ribosylation reversal. 对泛素 ADP- 核糖逆转机制的见解。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240896
Zhengrui Zhang, Chittaranjan Das
{"title":"Insights into mechanisms of ubiquitin ADP-ribosylation reversal.","authors":"Zhengrui Zhang, Chittaranjan Das","doi":"10.1042/BST20240896","DOIUrl":"10.1042/BST20240896","url":null,"abstract":"<p><p>Ubiquitination and ADP-ribosylation are two types of post-translational modification (PTM) involved in regulating various cellular activities. In a striking example of direct interplay between ubiquitination and ADP-ribosylation, the bacterial pathogen Legionella pneumophila uses its SidE family of secreted effectors to catalyze an NAD+-dependent phosphoribosyl ubiquitination of host substrates in a process involving the intermediary formation of ADP-ribosylated ubiquitin (ADPR-Ub). This noncanonical ubiquitination pathway is finely regulated by multiple Legionella effectors to ensure a balanced host subjugation. Among the various regulatory effectors, the macrodomain effector MavL has been recently shown to reverse the Ub ADP-ribosylation and regenerate intact Ub. Here, we briefly outline emerging knowledge on ubiquitination and ADP-ribosylation and tap into cases of direct cross-talk between these two PTMs. The chemistry of ADP-ribose in the context of the PTM and the reversal mechanisms of ADP-ribosylation are then highlighted. Lastly, focusing on recent structural studies on the MavL-mediated reversal of Ub ADP-ribosylation, we strive to deduce distinct mechanisms regarding the catalysis and product release of this reaction.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2525-2537"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709192","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
Insights into the regulation of mRNA translation by scaffolding proteins. 支架蛋白对mRNA翻译的调控。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20241021
Madeleine R Smith, Guilherme Costa
{"title":"Insights into the regulation of mRNA translation by scaffolding proteins.","authors":"Madeleine R Smith, Guilherme Costa","doi":"10.1042/BST20241021","DOIUrl":"10.1042/BST20241021","url":null,"abstract":"<p><p>Regionalisation of molecular mechanisms allows cells to fine-tune their responses to dynamic environments. In this context, scaffolds are well-known mediators of localised protein activity. These phenomenal proteins act as docking sites where pathway components are brought together to ensure efficient and reliable flow of information within the cell. Although scaffolds are mostly understood as hubs for signalling communication, some have also been studied as regulators of mRNA translation. Here, we provide a brief overview of the work unravelling how scaffolding proteins facilitate the cross-talk between the two processes. Firstly, we examine the activity of AKAP1 and AKAP12, two signalling proteins that not only have the capacity to anchor mRNAs to membranes but can also regulate protein synthesis. Next, we review the studies that uncovered how the ribosome-associated protein RACK1 orchestrates translation initiation. We also discuss the evidence pointing to the scaffolds Ezrin and LASP1 as regulators of early translation stages. In the end, we conclude with some open questions and propose future directions that will bring new insights into the regulation of mRNA translation by scaffolding proteins.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2569-2578"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783960","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
Untangling bacterial DNA topoisomerases functions. 解开细菌 DNA 拓扑异构酶的功能。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20240089
Céline Borde, Lisa Bruno, Olivier Espéli
{"title":"Untangling bacterial DNA topoisomerases functions.","authors":"Céline Borde, Lisa Bruno, Olivier Espéli","doi":"10.1042/BST20240089","DOIUrl":"10.1042/BST20240089","url":null,"abstract":"<p><p>Topoisomerases are the main enzymes capable of resolving the topological constraints imposed by DNA transactions such as transcription or replication. All bacteria possess topoisomerases of different types. Although bacteria with circular replicons should encounter similar DNA topology issues, the distribution of topoisomerases varies from one bacterium to another, suggesting polymorphic functioning. Recently, several proteins restricting, enhancing or modifying the activity of topoisomerases were discovered, opening the way to a new area of understanding DNA topology management during the bacterial cell cycle. In this review, we discuss the distribution of topoisomerases across the bacterial phylum and current knowledge on the interplay among the different topoisomerases to maintain topological homeostasis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2321-2331"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602651","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
Unusual modes of cell and nuclear divisions characterise Drosophila development. 果蝇的发育具有不寻常的细胞和核分裂模式。
IF 3.8 3区 生物学
Biochemical Society transactions Pub Date : 2024-12-19 DOI: 10.1042/BST20231341
Qiaolin Yang, Fernando Wijaya, Ridam Kapoor, Harshaa Chandrasekaran, Siddhant Jagtiani, Izaac Moran, Gary R Hime
{"title":"Unusual modes of cell and nuclear divisions characterise Drosophila development.","authors":"Qiaolin Yang, Fernando Wijaya, Ridam Kapoor, Harshaa Chandrasekaran, Siddhant Jagtiani, Izaac Moran, Gary R Hime","doi":"10.1042/BST20231341","DOIUrl":"10.1042/BST20231341","url":null,"abstract":"<p><p>The growth and development of metazoan organisms is dependent upon a co-ordinated programme of cellular proliferation and differentiation, from the initial formation of the zygote through to maintenance of mature organs in adult organisms. Early studies of proliferation of ex vivo cultures and unicellular eukaryotes described a cyclic nature of cell division characterised by periods of DNA synthesis (S-phase) and segregation of newly synthesized chromosomes (M-phase) interspersed by seeming inactivity, the gap phases, G1 and G2. We now know that G1 and G2 play critical roles in regulating the cell cycle, including monitoring of favourable environmental conditions to facilitate cell division, and ensuring genomic integrity prior to DNA replication and nuclear division. M-phase is usually followed by the physical separation of nascent daughters, termed cytokinesis. These phases where G1 leads to S phase, followed by G2 prior to M phase and the subsequent cytokinesis to produce two daughters, both identical in genomic composition and cellular morphology are what might be termed an archetypal cell division. Studies of development of many different organs in different species have demonstrated that this stereotypical cell cycle is often subverted to produce specific developmental outcomes, and examples from over 100 years of analysis of the development of Drosophila melanogaster have uncovered many different modes of cell division within this one species.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2281-2295"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602790","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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