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Annual review of biochemistry最新文献

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Unexpected Applications of AlphaFold in Molecular Sciences. AlphaFold在分子科学中的意外应用。
IF 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub Date: 2026-03-09 DOI: 10.1146/annurev-biochem-051424-071952
Jian Jiang, Guilin Wang, Daixin Li, Nicole Hayes, Benjamin Jones, Yazhou Shi, Huahai Qiu, Bengong Zhang, Tianshou Zhou, Guo-Wei Wei
{"title":"Unexpected Applications of AlphaFold in Molecular Sciences.","authors":"Jian Jiang, Guilin Wang, Daixin Li, Nicole Hayes, Benjamin Jones, Yazhou Shi, Huahai Qiu, Bengong Zhang, Tianshou Zhou, Guo-Wei Wei","doi":"10.1146/annurev-biochem-051424-071952","DOIUrl":"10.1146/annurev-biochem-051424-071952","url":null,"abstract":"<p><p>AlphaFold, a groundbreaking artificial intelligence model developed by DeepMind, has transformed the field of structural biology by predicting protein structures with unprecedented accuracy. Despite its widespread recognition and application across academia and industry, comprehensive reviews detailing AlphaFold's unexpected applications within the molecular sciences remain scarce. In this review, we critically examine AlphaFold's emerging roles across diverse molecular scientific disciplines. Specifically, we highlight its applications in enzyme engineering and drug development, nucleic acid modeling and vaccine design, the development of protein-based materials and targeted drug delivery systems, and modeling of complex systems and biological networks. To conclude, the review outlines potential future developments and enduring challenges within the application of AlphaFold to molecular sciences. Overall, this review aims to systematically analyze the most recent advances; explore novel interdisciplinary applications of AlphaFold within the realms of biology, chemistry, and materials science; and offer insights into future directions for research and application.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"55-80"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389118","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
Mitochondrial Precursor Overaccumulation Stress. 线粒体前体过度积累应激。
IF 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub Date: 2026-03-20 DOI: 10.1146/annurev-biochem-051424-061016
Liam P Coyne, Xin Jie Chen
{"title":"Mitochondrial Precursor Overaccumulation Stress.","authors":"Liam P Coyne, Xin Jie Chen","doi":"10.1146/annurev-biochem-051424-061016","DOIUrl":"10.1146/annurev-biochem-051424-061016","url":null,"abstract":"<p><p>Damage to mitochondria imparts multifaceted cellular stress that extends beyond bioenergetic deficit. One newly emerged example is mitochondrial precursor overaccumulation stress (mPOS). mPOS is marked by impaired mitochondrial protein import, causing the toxic accumulation and aggregation of unimported mitochondrial precursor proteins in the cytosol. Analogous to the well-studied endoplasmic reticulum stress, which blocks proteins from leaving the cell, mPOS can impose a drastic proteostatic burden in the cytosol and closely interconnects with cell signaling pathways. Here, we review how researchers discovered mPOS and discuss its central importance in several major mitochondria-induced stress signaling pathways. We then focus on the emerging field of mPOS in cell demise and human disease, and we present recent evidence that mPOS can affect cell fitness and survival independent of bioenergetics. Looking forward, mPOS may provide a complementary or alternative pathogenic mechanism to bioenergetic deficit for classic mitochondriopathy and many aging-associated degenerative diseases involving mitochondrial stress.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"401-429"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490360","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
The Semantics and Mechanisms of Enhancers and Promoters: "What Is True for E. coli Is True for the Elephant, Only More So". 增强子和启动子的语义和机制：“对大肠杆菌是正确的，对大象也是正确的，只是更正确”。
IF 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub Date: 2026-03-20 DOI: 10.1146/annurev-biochem-080125-014150
Kevin Struhl
{"title":"The Semantics and Mechanisms of Enhancers and Promoters: \"What Is True for <i>E. coli</i> Is True for the Elephant, Only More So\".","authors":"Kevin Struhl","doi":"10.1146/annurev-biochem-080125-014150","DOIUrl":"10.1146/annurev-biochem-080125-014150","url":null,"abstract":"<p><p>Three fundamental classes of gene regulatory elements were identified in <i>Escherichia coli</i> in the 1960s: operators bound by repressor proteins, promoters bound by the basic transcription machinery, and enhancers bound by activator proteins. Promoters mediate constitutive gene expression, whereas operators and enhancers regulate expression in response to physiological conditions. As discovered in the 1980s, interactions between proteins associated with spatially separated elements can loop out the intervening DNA and regulate transcription. Eukaryotic gene regulation is mediated by the same three classes of genetic elements, but due to semantic confusion, it is often believed the eukaryotic enhancers activate transcription from long distances via enhancer-promoter loops. However, eukaryotic enhancers mediate only local changes in chromatin, and they stimulate transcription via directional and short-range interactions with the basic RNA polymerase II machinery at promoters. Enhancer action at a distance is mediated by loops between proximal and distal enhancers that bring activator proteins associated with distal enhancers in proximity to promoters. Thus, Jacques Monod's 1954 conjecture that \"what is true for <i>E. coli</i> is true for the elephant, only more so\" has proven correct.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"199-219"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490386","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
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 20.5 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":20.5,"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 20.5 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":20.5,"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 24.9 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":24.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472483/pdf/","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":"OA","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 20.5 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":20.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12893018/pdf/","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":"OA","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 24.9 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":24.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404299/pdf/","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":"OA","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 20.5 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":20.5,"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 20.5 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":20.5,"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
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