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Annual review of biochemistry最新文献

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Membrane Protein Complexity Revealed Through Native Mass Spectrometry. 通过天然质谱法揭示膜蛋白的复杂性。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-03-24 DOI: 10.1146/annurev-biochem-081424-044501
Sophie A S Lawrence, Andrew Dolan, Maya M Miller, Carol V Robinson
{"title":"Membrane Protein Complexity Revealed Through Native Mass Spectrometry.","authors":"Sophie A S Lawrence, Andrew Dolan, Maya M Miller, Carol V Robinson","doi":"10.1146/annurev-biochem-081424-044501","DOIUrl":"10.1146/annurev-biochem-081424-044501","url":null,"abstract":"<p><p>In all living organisms, membrane proteins play a crucial role in governing essential biological functions, such as cellular signaling and molecular transport. These functions rely on intricate interactions with a variety of biomolecules, including substrates, proteins, metabolites, and lipids. Any disruption or alteration to these interactions can result in disease. Therefore, comprehending the complex assemblies of membrane proteins, and their intrinsic interactions, is crucial for unraveling the mechanisms of cellular regulation and has implications in disease pathology. Over the past three decades, native mass spectrometry (MS) has emerged as a pivotal tool for investigating the structure and dynamics of proteins, including membrane protein complexes. In this review, we discuss recent developments in instrumentation that advance our ability to characterize membrane proteins in their native context. As we transition toward increasingly complex eukaryotic systems, we show how this information is translated into an understanding of disease. We also highlight preliminary studies in which native MS has been used to sequence and localize membrane protein complexes within endogenous tissue. This level of detail offers the promise of informing about the molecular mechanisms of disease states.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"111-135"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Mechanisms of General Anesthesia. 全身麻醉的机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1146/annurev-biochem-030222-121430
Scott B Hansen
{"title":"Mechanisms of General Anesthesia.","authors":"Scott B Hansen","doi":"10.1146/annurev-biochem-030222-121430","DOIUrl":"10.1146/annurev-biochem-030222-121430","url":null,"abstract":"<p><p>Anesthetics are a chemically diverse collection of molecules that dictate neuronal excitability and form the basis of modern medicine. Their molecular mechanism of action is fundamental to understanding nerve excitability, mood, consciousness, and psychiatric disease. Sites of anesthetic action are located within ion channels and the plasma membrane. In the membrane, palmitate, a 16-carbon lipid, covalently links proteins and binds a lipid site to allow anesthetic sensitivity. In ion channels, anesthetics bind within an allosteric conduction pathway or compete for binding of regulatory lipids. Mechanisms of action arising from these binding sites share structural and functional characteristics with the classic anesthetic site in the enzyme luciferase. An update on the Meyer-Overton correlation is reviewed relative to each mechanism and placed in historical context with early theories. The review ends with a discussion of unresolved questions, including questions concerning endogenous anesthetics, anesthetic stereoselectivity, and aspects of a chain-length cutoff.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"503-530"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Structural Mechanisms of Topoisomerase-Targeting Drugs. 拓扑异构酶靶向药物的结构机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-05-26 DOI: 10.1146/annurev-biochem-030122-043917
Anthony C O'Donnell, James M Berger
{"title":"Structural Mechanisms of Topoisomerase-Targeting Drugs.","authors":"Anthony C O'Donnell, James M Berger","doi":"10.1146/annurev-biochem-030122-043917","DOIUrl":"10.1146/annurev-biochem-030122-043917","url":null,"abstract":"<p><p>Topoisomerases are enzymes responsible for recognizing and resolving superhelical crossings and topological tangles in DNA. Topoisomerases also serve as valuable established targets for numerous clinically used antibacterial and antitumor agents; small-molecule antagonists not only have an ability to disrupt essential cellular functions but also convert these enzymes into DNA-damaging agents. Here, we review biochemical and structural data that explain how current therapeutics target eukaryotic and prokaryotic topoisomerases at a molecular level. New and highly promising agents that showcase the continued utility of targeting topoisomerases for clinical benefit are also discussed.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"223-251"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Essential Biology of Lipid Droplets. 脂滴的基本生物学。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1146/annurev-biochem-091724-013733
Robert V Farese, Tobias C Walther
{"title":"Essential Biology of Lipid Droplets.","authors":"Robert V Farese, Tobias C Walther","doi":"10.1146/annurev-biochem-091724-013733","DOIUrl":"10.1146/annurev-biochem-091724-013733","url":null,"abstract":"<p><p>Lipid droplets (LDs), long overlooked as inert cellular storage organelles, are now recognized for their complex and rich biology as membraneless organelles integral to cell metabolism. Significant advances have revealed that LDs are crucial for cellular processes that include the storage and retrieval of lipids for metabolic energy and membrane synthesis and the detoxification of lipids by sequestering them in the organelle's core. Here, we review key aspects of LD biology, emphasizing insights into fundamental mechanisms of their formation, the mechanisms of protein targeting, new insights into LD turnover, and how LDs integrate into cellular metabolism. Where possible, we describe how these processes are important in physiology and how alterations in LD biology can lead to metabolic disease. We highlight unresolved questions and key challenges to be addressed for further advancing our understanding of LD biology and its implications for health and disease.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"447-477"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
DNA Damage and Replication Stress Checkpoints. DNA损伤和复制压力检查点。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 DOI: 10.1146/annurev-biochem-072324-031915
Luke A Yates, Xiaodong Zhang, Peter M Burgers
{"title":"DNA Damage and Replication Stress Checkpoints.","authors":"Luke A Yates, Xiaodong Zhang, Peter M Burgers","doi":"10.1146/annurev-biochem-072324-031915","DOIUrl":"10.1146/annurev-biochem-072324-031915","url":null,"abstract":"<p><p>DNA damage checkpoints are key regulatory signaling cascades that arrest cell cycle progression upon DNA damage or upon DNA replication stalling and allow time for repair or correction. Failure to elicit these checkpoints can lead to genomic instability that can result in cell death or mutations, ultimately leading to diseases such as cancer. Components of the DNA damage checkpoint are attractive targets for precision medicine to treat cancers. Over the last several years, cutting-edge structural techniques have provided molecular insights into the highly coordinated checkpoint signaling that occurs in response to DNA damage or other obstacles to replication progression. This review summarizes our current mechanistic understanding of the DNA damage checkpoint in eukaryotes, with an emphasis on the sensor kinases ATM (Tel1) and ATR (Mec1), highlighting structure-function and cellular studies.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"94 1","pages":"195-221"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lipid Dynamics at Membrane Contact Sites. 膜接触部位的脂质动力学。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-03-11 DOI: 10.1146/annurev-biochem-083024-122821
Karin M Reinisch, Pietro De Camilli, Thomas J Melia
{"title":"Lipid Dynamics at Membrane Contact Sites.","authors":"Karin M Reinisch, Pietro De Camilli, Thomas J Melia","doi":"10.1146/annurev-biochem-083024-122821","DOIUrl":"10.1146/annurev-biochem-083024-122821","url":null,"abstract":"<p><p>In eukaryotes, lipid building blocks for cellular membranes are made largely in the endoplasmic reticulum and then redistributed to other organelles. Lipids are transported between organelles by vesicular trafficking or else by proteins located primarily at sites where different organelles are closely apposed. Here we discuss transport at organelle contact sites mediated by shuttle-like proteins that carry single lipids between membranes to fine-tune their composition and by the more recently discovered bridge-like proteins that tether two organelles and provide a path for bulk lipid movement. Protein-mediated lipid transport is assisted by integral membrane proteins that have roles in (<i>a</i>) lowering the energy barrier for lipid transfer between the membrane and the lipid transfer protein, a key parameter determining the transfer rate, and (<i>b</i>) scrambling lipids to counteract the bilayer asymmetry that would result from such transfer. Advances in this field are shedding new light on a variety of physiological mechanisms.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"479-502"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Extracellular Vesicles and Cellular Homeostasis. 细胞外囊泡与细胞稳态。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-03-18 DOI: 10.1146/annurev-biochem-100924-012717
Jordan Matthew Ngo, Justin Krish Williams, Congyan Zhang, Amr Hosny Saleh, Xiao-Man Liu, Liang Ma, Randy Schekman
{"title":"Extracellular Vesicles and Cellular Homeostasis.","authors":"Jordan Matthew Ngo, Justin Krish Williams, Congyan Zhang, Amr Hosny Saleh, Xiao-Man Liu, Liang Ma, Randy Schekman","doi":"10.1146/annurev-biochem-100924-012717","DOIUrl":"10.1146/annurev-biochem-100924-012717","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are secreted, membrane-enclosed particles that have been proposed to play a broad role in intercellular communication. Most often, EVs, by analogy to enveloped viruses, are suggested to fuse to or within a target cell to deliver a soluble signaling molecule into the cytoplasm. However, significant evidence supports an alternative model in which EVs are secreted to promote homeostasis. In this model, EVs are loaded with unwanted or toxic cargo, secreted upon cellular or organismal stress, and degraded by other cells. Here, we present evidence supporting this homeostatic EV model and discuss the general inefficiency of EV cargo delivery. While the homeostatic and viral delivery models for EV function are not mutually exclusive, we propose that much of the evidence presented is hard to reconcile with a broad role for EVs in cargo transfer as a means to promote intercellular communication.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"587-609"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Paternal Effects in Mammals: Challenges and Opportunities. 哺乳动物的父系效应：挑战与机遇。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-03-31 DOI: 10.1146/annurev-biochem-072924-013858
Chih-Hsiang Yang, Oliver J Rando
{"title":"Paternal Effects in Mammals: Challenges and Opportunities.","authors":"Chih-Hsiang Yang, Oliver J Rando","doi":"10.1146/annurev-biochem-072924-013858","DOIUrl":"10.1146/annurev-biochem-072924-013858","url":null,"abstract":"<p><p>Once considered heretical, the idea that environmental conditions experienced in one generation can influence traits in future generations is now increasingly accepted. In particular, hundreds of studies in mammals have documented effects of various paternal exposures on offspring metabolism, behavior, and disease susceptibility. While the core claim that a father's experiences can modulate offspring health and disease is now well-established, the mechanistic basis for paternal effects in mammals remains obscure despite nearly two decades of intensive investigation. Here, we briefly review the phenomenology of mammalian paternal effects in broad strokes, focusing on common themes across the literature. We then critically explore our current understanding of the sperm epigenome and discuss challenges to the dominant mechanistic hypotheses proposed in the paternal effects literature.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"253-278"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Silencing by the HUSH Epigenetic Transcriptional Repressor Complex. 表观遗传转录抑制复合物的沉默作用。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 DOI: 10.1146/annurev-biochem-020425-045352
Paul J Lehner
{"title":"Silencing by the HUSH Epigenetic Transcriptional Repressor Complex.","authors":"Paul J Lehner","doi":"10.1146/annurev-biochem-020425-045352","DOIUrl":"10.1146/annurev-biochem-020425-045352","url":null,"abstract":"<p><p>Retroviral and retrotransposon invasion pose a constant threat to genome integrity and have driven the evolution of host defense pathways able to counter these attacks. The human silencing hub (HUSH complex) is an epigenetic transcriptional repressor complex that recognizes and silences newly integrated retroelements through the establishment of ectopic heterochromatin and chromatin compaction. HUSH provides a genome-wide immunosurveillance system whose challenging task is to detect and silence any newly integrated retroelements, and it thus plays a key role in host defense. To distinguish self from nonself genomic DNA, HUSH recognizes long single-exon (intronless) DNA, the essential hallmark of reverse transcription. Retroelements, being RNA derived, lack classical, noncoding cellular introns, so a long, intronless sequence of DNA is the abnormal molecular pattern that allows HUSH to distinguish invading retroelements from intron-containing host genes. As a newly identified component of the innate immune system, HUSH protects the genome from the reverse flow of genetic information from RNA to DNA, revealing an unanticipated mechanism of postintegration genome immunity.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"94 1","pages":"361-386"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Eukaryotic Microproteins. 真核Microproteins。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-06-01 Epub Date: 2025-04-17 DOI: 10.1146/annurev-biochem-080124-012840
Nadiya Jaunbocus, Valerie Ebenki, Haomiao Su, Sarah A Slavoff
{"title":"Eukaryotic Microproteins.","authors":"Nadiya Jaunbocus, Valerie Ebenki, Haomiao Su, Sarah A Slavoff","doi":"10.1146/annurev-biochem-080124-012840","DOIUrl":"10.1146/annurev-biochem-080124-012840","url":null,"abstract":"<p><p>Microproteins are polypeptides of 100-150 amino acids or fewer that have not been annotated by genome annotation consortia, given their small size and other noncanonical properties. Translated microproteins are now known to number in the thousands in the human genome, to function in critical cellular and physiological processes, and to be dysregulated or mutated in diseases including neurodegeneration and cancer. Knowledge about microproteins has rapidly accumulated since the advent of ribosome profiling enabled their global discovery 15 years ago. In this review, we summarize what is known about eukaryotic microprotein discovery, the sequences and expression mechanisms of small open reading frames, and microprotein functions from yeast to human.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"1-28"},"PeriodicalIF":12.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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