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Annual review of biochemistry最新文献

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Nucleocytoplasmic Transport. 核质运输。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-09 DOI: 10.1146/annurev-biochem-031622-025802
George W Mobbs, Stefan Petrovic, André Hoelz
{"title":"Nucleocytoplasmic Transport.","authors":"George W Mobbs, Stefan Petrovic, André Hoelz","doi":"10.1146/annurev-biochem-031622-025802","DOIUrl":"10.1146/annurev-biochem-031622-025802","url":null,"abstract":"<p><p>Compartmentalization of the genome within the nucleus of eukaryotic cells emerged alongside a two-component molecular machinery for selective transport of macromolecules: a static yet conformationally flexible channel formed by the ∼120-MDa nuclear pore complex (NPC), which generates a size-selective diffusion barrier, and a mobile machinery of transport factors and adapters that recognize and ferry macromolecular cargoes across this barrier. Here, we trace the historical development of the nucleocytoplasmic transport field, from early biochemical identification of transport components to contemporary structural and functional insights. We examine how decades of research have illuminated the principles of cargo recognition, the relationship between transport factor structure and function, and the mechanisms that enable unidirectional import and export. The review concludes by highlighting emerging questions about messenger RNA export pathways, mechanosensitive regulation of NPC function, and the role of nucleocytoplasmic transport in health and disease.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643949","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
Packaging of Single-Stranded RNA in Viruses and Virus-Like Particles. 单链RNA在病毒和病毒样颗粒中的包装。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-08 DOI: 10.1146/annurev-biochem-080525-105928
Rees F Garmann, William M Gelbart
{"title":"Packaging of Single-Stranded RNA in Viruses and Virus-Like Particles.","authors":"Rees F Garmann, William M Gelbart","doi":"10.1146/annurev-biochem-080525-105928","DOIUrl":"10.1146/annurev-biochem-080525-105928","url":null,"abstract":"<p><p>Our double-stranded DNA (dsDNA) genomes are famously compacted by proteins in the nuclei of our cells, resulting in meters of dsDNA being confined in micron-sized volumes. The most prevalent form of viral genomes, however, is single-stranded RNA (ssRNA), which is compacted at significantly higher density in protective protein shells with nanometer dimensions. In this review, we discuss the special nature of ssRNA that allows it to be spontaneously packaged in this way by co-self-assembly with viral capsid protein (CP). We focus on the few viruses whose nucleocapsids can be reconstituted from their purified CP and ssRNA genomes and whose CPs can spontaneously package heterologous RNA into virus-like particles (VLPs). These VLPs are then compared with their cell-synthesized versions, with lentivirus and adeno-associated virus vector particles, and with nucleocapsids formed by nonviral proteins whose messenger RNAs are put under directed evolutionary pressure to be packaged by them in cellulo.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637756","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
Shaping of the Infant Gut Microbiome by Milk Oligosaccharides. 牛奶低聚糖对婴儿肠道微生物群的塑造。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-08 DOI: 10.1146/annurev-biochem-051024-062915
Victoria A Federico, David E Cliffel, Jennifer A Gaddy, Steven D Townsend
{"title":"Shaping of the Infant Gut Microbiome by Milk Oligosaccharides.","authors":"Victoria A Federico, David E Cliffel, Jennifer A Gaddy, Steven D Townsend","doi":"10.1146/annurev-biochem-051024-062915","DOIUrl":"10.1146/annurev-biochem-051024-062915","url":null,"abstract":"<p><p>The gut microbiome governs aspects of human growth and development. While human milk's primary purpose is metabolism, it also provides nonnutritious biologics and macromolecules. This mixture includes the human milk oligosaccharides (HMOs), which are indigestible and survive the low pH of the stomach and small intestine, reaching the large intestine intact. Here, HMOs serve as prebiotics for beneficial bacteria, providing a competitive growth advantage over potential pathogens. Upon metabolizing HMOs, commensals generate short-chain fatty acids and metabolites that enhance the gut community. Therefore, HMOs work to develop and sustain the gut microbial community as a living therapeutic that prevents illness from potential microbial pathogens and modulates development of the infant gut. The goal of this targeted review is to characterize the roles HMOs play in governing bacterial and viral members of the infant gut microbiome, describing how HMOs both define a healthy microbiota and prevent microbial dysbiosis.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637698","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
Proteostasis Deregulation by Metabolism Drives the Hallmarks of Cancer. 代谢导致的蛋白质平衡失调驱动癌症的特征。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-03 DOI: 10.1146/annurev-biochem-051424-052148
Ashok R Venkitaraman
{"title":"Proteostasis Deregulation by Metabolism Drives the Hallmarks of Cancer.","authors":"Ashok R Venkitaraman","doi":"10.1146/annurev-biochem-051424-052148","DOIUrl":"https://doi.org/10.1146/annurev-biochem-051424-052148","url":null,"abstract":"<p><p>Cancer cells acquire hallmark behaviors through adaptations that extend beyond genetic and epigenetic changes. Proteostasis-the biochemical network governing protein synthesis, folding, trafficking, and degradation-is a fundamental, yet underappreciated, mediator of these adaptations that merits consideration as a hallmark-enabling mechanism. Metabolic alterations impose proteotoxic stress, globally rewire protein homeostasis, and selectively modulate key oncogenic and tumor suppressive proteins. A unifying framework is proposed wherein metabolic deregulation of proteostasis operates throughout carcinogenesis: early, by enhancing accumulation of premalignant clones bearing cancer-driving somatic mutations in response to environmental and systemic metabolic stress, and later, by buffering proteotoxic stress to sustain malignant growth in hostile tissue environments. This perspective connects cancer risk with genetic background, diet, microbiome-derived metabolites, and metabolic disease, introduces metabolic bypass of tumor suppression as an alternative to classical genetic models, and highlights the metabolism-proteostasis interface as a promising target for cancer prevention and therapy.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615671","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
JoAnne Stubbe's Radical Path: A Story of Passion, Curiosity, and Persistence. 乔安妮·斯塔比的激进之路：一个关于激情、好奇心和坚持的故事。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-02 DOI: 10.1146/annurev-biochem-040320-103623
Mary O'Reilly, JoAnne Stubbe
{"title":"JoAnne Stubbe's Radical Path: A Story of Passion, Curiosity, and Persistence.","authors":"Mary O'Reilly, JoAnne Stubbe","doi":"10.1146/annurev-biochem-040320-103623","DOIUrl":"10.1146/annurev-biochem-040320-103623","url":null,"abstract":"<p><p>Massachusetts Institute of Technology Professor Emerita JoAnne Stubbe was the chair of Mary O'Reilly's thesis committee. Over a decade later, they became neighbors, and then a global pandemic made them friends. Here they attempt to summarize JoAnne's life and her life's work-a story of passion, curiosity, and persistence, all for the thrill of discovery. Though, it may be premature: She is not done yet.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589455","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
From Cancer, Malate-Aspartate Shuttle, RNA Replicase, and mtDNA to Trypanosomes and Back to Cancer Again. 从癌症，苹果酸-天冬氨酸穿梭，RNA复制酶和mtDNA到锥虫，再回到癌症。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-04-01 DOI: 10.1146/annurev-biochem-051424-083457
Piet Borst
{"title":"From Cancer, Malate-Aspartate Shuttle, RNA Replicase, and mtDNA to Trypanosomes and Back to Cancer Again.","authors":"Piet Borst","doi":"10.1146/annurev-biochem-051424-083457","DOIUrl":"https://doi.org/10.1146/annurev-biochem-051424-083457","url":null,"abstract":"<p><p>I studied medicine to become an endocrinologist but ended up in biochemistry. As a graduate student, I studied tumor mitochondria and discovered the malate-aspartate shuttle (the major route in animal cells for shuttling reducing equivalents into mitochondria). As a postdoc in New York, I switched to the replication of RNA bacteriophages, and on my return to Amsterdam, I started on mitochondrial biogenesis and discovered the circular mitochondrial DNAs (mtDNAs) of animal mitochondria and yeast. I also tackled trypanosomatids, major parasites of humans, in which we characterized their exotic mtDNA networks and discovered the glycosome, an organelle containing most of the glycolytic system. We helped to unravel the mechanism of antigenic variation in African trypanosomes and even discovered a new base, base J, in the DNA of trypanosomatids.After moving to the Netherlands Cancer Institute, I combined the trypanosomatids with a project on mechanisms of multidrug resistance in cancer cells. In particular, studying mice with one or more disrupted ABC transporter genes resulted in interesting findings in drug pharmacokinetics and in the elucidation of the cause of two inborn errors.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589482","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
Radical Chemistry in Metalloenzymes: Bridging Inorganic Centers and Biological Catalysis. 金属酶的自由基化学：桥接无机中心和生物催化。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-03-30 DOI: 10.1146/annurev-biochem-051024-013029
Maximilian Böhm, Fikret Mamedov, Gustav Berggren, Martin Högbom
{"title":"Radical Chemistry in Metalloenzymes: Bridging Inorganic Centers and Biological Catalysis.","authors":"Maximilian Böhm, Fikret Mamedov, Gustav Berggren, Martin Högbom","doi":"10.1146/annurev-biochem-051024-013029","DOIUrl":"https://doi.org/10.1146/annurev-biochem-051024-013029","url":null,"abstract":"<p><p>Radical chemistry, once deemed too reactive for biological systems, is delicately controlled within metalloenzymes to catalyze challenging chemical transformations under physiological conditions. This review explores the diverse strategies employed by metalloenzymes to generate, stabilize, and utilize highly reactive radical intermediates. We discuss amino acid-based radicals (tyrosyl, tryptophan, cysteinyl, glycyl, and DOPA), radicals derived from molecular oxygen (in heme, manganese, copper, and nonheme iron enzymes), and cofactor-based radicals (specifically adenosylcobalamin and radical <i>S</i>-adenosylmethionine enzymes). We devote special attention to ribonucleotide reductases as a prime example of evolutionary convergence of radical mechanisms. The interplay among redox-active cofactors, metal ions, and protein scaffolds highlights nature's ingenuity in generating, controlling, and utilizing radicals. We also discuss emerging themes and open questions, emphasizing how advances in structural and spectroscopic techniques continue to deepen our understanding of these complex and vital enzymatic processes.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580343","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
Membrane Protein Insertion in Mammalian Cells. 哺乳动物细胞中的膜蛋白插入。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-03-30 DOI: 10.1146/annurev-biochem-080125-020218
Alina Guna, Vy N Nguyen, Taylor A Stevens, Rebecca M Voorhees
{"title":"Membrane Protein Insertion in Mammalian Cells.","authors":"Alina Guna, Vy N Nguyen, Taylor A Stevens, Rebecca M Voorhees","doi":"10.1146/annurev-biochem-080125-020218","DOIUrl":"https://doi.org/10.1146/annurev-biochem-080125-020218","url":null,"abstract":"<p><p>Integral membrane proteins play critical roles in mammalian cells, ranging from mediating cell-cell interactions to regulating apoptosis. These increasingly diverse functions necessitated the evolution of membrane proteins with more complex biophysical properties and architectures. In turn, specialized complexes called insertases have coevolved to integrate these proteins into the appropriate lipid bilayer. Notably, key sites of membrane protein biogenesis such as the endoplasmic reticulum and the outer and inner membranes of the mitochondria rely on distinct sets of insertases that work in concert, each specializing in membrane protein segments with particular features or properties. Here, we describe recent discoveries that shed light both on the molecular mechanisms of these insertases and on the many distinct pathways required for the insertion and folding of the mammalian membrane proteome.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580410","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
Endogenous Sources of Abasic Sites and Implications for DNA Replication: Mechanisms of Fork Stalling and Recovery. 基本位点的内源性来源及其对DNA复制的影响：分叉失速和恢复的机制。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-03-30 DOI: 10.1146/annurev-biochem-030222-114544
Angelo Taglialatela, Alberto Ciccia
{"title":"Endogenous Sources of Abasic Sites and Implications for DNA Replication: Mechanisms of Fork Stalling and Recovery.","authors":"Angelo Taglialatela, Alberto Ciccia","doi":"10.1146/annurev-biochem-030222-114544","DOIUrl":"10.1146/annurev-biochem-030222-114544","url":null,"abstract":"<p><p>Apurinic/apyrimidinic (AP) sites, also known as abasic sites, are among the most frequent DNA lesions, arising spontaneously or as intermediates in base excision repair. Their structural impediment to DNA replication fork progression, lack of coding information, and conversion into strand breaks constitute a threat and can lead to genome instability if not properly managed. This review examines the impact of AP sites on DNA replication, detailing mechanisms of lesion bypass, including translesion synthesis, template switching, and repriming of DNA synthesis. We highlight protective pathways that shield AP sites from nucleolytic attack and explore how endogenous processes such as uracil excision, cytosine methylation, and oxidative damage generate these lesions. By integrating biochemical and cellular perspectives, we present a comprehensive view of how cells replicate their DNA in the presence of AP sites and how their mismanagement contributes to replication stress, mutagenesis, and disease.Updated on April 15, 2026.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580364","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
Cotranslational Assembly of Oligomeric Proteins. 低聚蛋白的共翻译组装。
IF 20.5 1区 生物学
Annual review of biochemistry Pub Date : 2026-03-25 DOI: 10.1146/annurev-biochem-051024-124747
Jaime Santos, Sander J Tans, Nenad Ban, Günter Kramer, Bernd Bukau
{"title":"Cotranslational Assembly of Oligomeric Proteins.","authors":"Jaime Santos, Sander J Tans, Nenad Ban, Günter Kramer, Bernd Bukau","doi":"10.1146/annurev-biochem-051024-124747","DOIUrl":"https://doi.org/10.1146/annurev-biochem-051024-124747","url":null,"abstract":"<p><p>The assembly of newly synthesized proteins into functionally active oligomers has long been regarded as a posttranslational process driven by random collision of subunits. However, growing evidence indicates that, for many proteins, assembly occurs cotranslationally, tightly coupling synthesis, folding, and subunit assembly. This fundamentally different mechanism enables the spatial and temporal coordination of assembly, promotes the hierarchical formation of multisubunit assemblies, enhances the stability of involved subunits, enlarges the space of feasible protein structures including complexes with intertwined subunits, and has profound effects on protein evolution and function. In this review, we describe the molecular mechanisms, cellular requirements, and functional implications of cotranslational assembly and discuss its relevance to human disease, its evolutionary significance, and its transformative potential in synthetic biology and recombinant protein production.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":20.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508827","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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