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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 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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":"549-567"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13163208/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate. 启动子-近端暂停：一个决定RNA聚合酶II命运的决定点。
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-051424-053703
Usman Hyder, David L Bentley
{"title":"The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate.","authors":"Usman Hyder, David L Bentley","doi":"10.1146/annurev-biochem-051424-053703","DOIUrl":"10.1146/annurev-biochem-051424-053703","url":null,"abstract":"<p><p>A signature feature of transcription on most genes in multicellular animals is that RNA polymerase II (RNAPII) piles up approximately 50 bases downstream of the start site at the promoter-proximal pause (PPP). Promoter-proximal pausing is controlled by positive and negative elongation factors that associate with RNAPII. There are two major outcomes for promoter-proximally paused RNAPII complexes: release into the gene body and premature termination. Here we discuss how RNAPII dynamics at the PPP function in a quality control checkpoint and in regulation of RNAPII flux through genes. We propose a pause release-attenuation model to describe RNAPII dynamics at the PPP.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"221-246"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490371","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
Nucleocytoplasmic Transport. 核质运输。
IF 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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":"247-290"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","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
The Human Autophagy Core Complexes. 人类自噬核心复合物。
IF 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub Date: 2026-03-25 DOI: 10.1146/annurev-biochem-072425-030036
James H Hurley
{"title":"The Human Autophagy Core Complexes.","authors":"James H Hurley","doi":"10.1146/annurev-biochem-072425-030036","DOIUrl":"10.1146/annurev-biochem-072425-030036","url":null,"abstract":"<p><p>The autophagy core machinery carries out the fundamental reactions of autophagosome biogenesis across all forms of bulk and selective macroautophagy. In humans, the core complexes consist of the ULK1 complex (ULK1C), the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1), the ATG8 proteins and the ATG8ylation machinery, the phosphatidylinositol 3-phosphate (PI3P)-sensing WIPI proteins, the lipid transporter ATG2, and the lipid scramblase and initiation scaffold ATG9. These complexes form a web of interactions that can be initiated by clustering of the FIP200 subunit of ULK1C but also by PI3KC3-C1 or WIPI2. Upon autophagy induction, these interactions are intensified by feed-forward signaling loops. These loops are amplified by WIPI-PI3P interactions and the conjugation of ATG8 proteins to the membrane by the ATG12-ATG5-ATG16L1 complex. Autophagosomes are seeded by ATG9 vesicles, which accrue initiation machinery on their surface and dock onto a PI3P-positive domain of the endoplasmic reticulum known as the omegasome. The omegasome contact site is the focal point for autophagosome growth, which is fed by lipid transport through the ATG2 bridge-like lipid transporter. The core complexes function in a dynamic manner, which makes autophagy vulnerable to stalling when dynamism fails. Disassembly and dissociation of the machinery, which is promoted at least in part by ULK1, is likely to be as important as assembly.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"507-524"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508830","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
Molecular Structure and Function of Zinc-Dependent Histone Deacetylases. 锌依赖性组蛋白去乙酰化酶的分子结构和功能。
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-051424-053005
David W Christianson
{"title":"Molecular Structure and Function of Zinc-Dependent Histone Deacetylases.","authors":"David W Christianson","doi":"10.1146/annurev-biochem-051424-053005","DOIUrl":"10.1146/annurev-biochem-051424-053005","url":null,"abstract":"<p><p>The eleven known zinc-dependent histone deacetylases (HDACs) catalyze the deacetylation or deacylation of myriad protein and small molecule substrates throughout the cell. The biological functions of HDACs are much more diverse than the name HDAC implies, but this name is nonetheless retained for historical purposes. The chemical mechanism of catalysis is generally conserved among HDAC isozymes: Electrophilic activation of the substrate is achieved by zinc coordination and hydrogen bonding, and nucleophilic activation of a zinc-bound water molecule is enhanced by a general base. Since aberrant activity is observed for specific HDAC isozymes in certain diseases, the development of isozyme-selective inhibitors is a current priority in worldwide medicinal chemistry campaigns. In this review, the biological functions and chemical mechanisms of the HDACs are discussed to establish the molecular context of catalysis and inhibition, particularly as the chemistry of catalysis is harnessed in the development of mechanism-based inhibitors.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"173-197"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490328","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 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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":"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":"347-370"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","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
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 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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":"1-27"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","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
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 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"143-172"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","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
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 24.9 1区 生物学
Annual review of biochemistry Pub Date : 2026-06-01 Epub 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":"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":"29-53"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","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
The Coronavirus Replication-Transcription Complex. 冠状病毒复制转录复合体
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-052621-091439
Ramakanth Madhugiri, Heiko Slanina, Raspudin Saleem-Batcha, John Ziebuhr
{"title":"The Coronavirus Replication-Transcription Complex.","authors":"Ramakanth Madhugiri, Heiko Slanina, Raspudin Saleem-Batcha, John Ziebuhr","doi":"10.1146/annurev-biochem-052621-091439","DOIUrl":"10.1146/annurev-biochem-052621-091439","url":null,"abstract":"<p><p>Coronaviruses (family <i>Coronaviridae</i>, order <i>Nidovirales</i>) include major human and animal pathogens. They have exceptionally large RNA genomes and use complex strategies to replicate and express these genomes. Intensive research activities in recent years have significantly advanced our knowledge of the molecular mechanisms involved in coronavirus RNA synthesis. Here, we briefly review these mechanisms and focus in particular on the structures and functions of the core replication-transcription complex (RTC) and other enzyme functions that can be recruited to this complex to fulfil additional functions, for example, in the context of 5' capping of viral mRNAs or in the context of mechanisms that control the processivity, replication fidelity, and backtracking of RTCs. Some of these recent studies provided fundamentally new insight into specific roles of previously identified genetic markers of coronaviruses and other nidoviruses, including specific functions in an unconventional RNA capping mechanism and potential roles in proofreading and discontinuous negative-strand RNA synthesis.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"317-346"},"PeriodicalIF":24.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490373","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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