EMBO Journal最新文献_第3页

Prothrombinase processivity is conferred by substrate allostery. 凝血酶原的加工性是由底物变构引起的。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-22 DOI: 10.1038/s44318-026-00782-4

Fatma Işık Üstok, Alexandre Faille, Alan J Warren, James A Huntington

引用次数: 0

MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin. MATCAP1优先结合扩展的微管蛋白构象产生去酪氨酸和ΔC2 α-微管蛋白。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-13 DOI: 10.1038/s44318-026-00772-6

Yang Yue, Takashi Hotta, Ryoma Ohi, Kristen J Verhey

{"title":"MATCAP1 preferentially binds an expanded tubulin conformation to generate detyrosinated and ΔC2 α-tubulin.","authors":"Yang Yue, Takashi Hotta, Ryoma Ohi, Kristen J Verhey","doi":"10.1038/s44318-026-00772-6","DOIUrl":"10.1038/s44318-026-00772-6","url":null,"abstract":"Microtubules are cytoskeletal filaments with critical roles in cell division, cell motility, intracellular trafficking, and cilium function. In cells, subsets of microtubules are selectively marked by posttranslational modifications (PTMs) that control the ability of microtubule-associated proteins (MAPs) and molecular motors to engage microtubules. Detyrosination (ΔY) and ΔC2 are PTMs of α-tubulin wherein one or two residues, respectively, are enzymatically removed from the C-terminus of the protein. How specific patterns of PTMs are generated in cells is incompletely understood. Here, we use in vitro reconstitution assays to investigate the microtubule-binding behavior of metallopeptidase MATCAP1 and the mechanism by which it generates ΔY and ΔC2 modifications of α-tubulin. We demonstrate that MATCAP1 preferentially binds to microtubules composed of tubulin subunits in an expanded conformation, which can be induced by preventing β-tubulin GTP hydrolysis, taxol treatment, or kinesin-1 stepping. MATCAP1 exhibits a long dwell-time on microtubules and sequentially removes residues to generate ΔY-microtubules and ΔC2-microtubules. Thus, the lattice conformation of microtubules is a key factor that gates the binding and activity of MATCAP1.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678286","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

Convergent evolution of aerobic fermentation through divergent mechanisms acting on key shared glycolytic genes. 通过作用于关键共享糖酵解基因的不同机制，有氧发酵的趋同进化。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-10 DOI: 10.1038/s44318-026-00778-0

Linda C Horianopoulos, Antonis Rokas, Chris Todd Hittinger

{"title":"Convergent evolution of aerobic fermentation through divergent mechanisms acting on key shared glycolytic genes.","authors":"Linda C Horianopoulos, Antonis Rokas, Chris Todd Hittinger","doi":"10.1038/s44318-026-00778-0","DOIUrl":"10.1038/s44318-026-00778-0","url":null,"abstract":"As the tree of life becomes increasingly accessible to molecular investigations, describing mechanisms underlying evolutionary convergence and constraint will be crucial to understanding diversification. The lineage including the model yeast Saccharomyces cerevisiae evolved aerobic fermentation in part through an ancient whole genome duplication and retention of glycolytic genes. To evaluate glycolytic rates across diverse yeasts, we developed and deployed an extracellular acidification rates (ECAR) assay on 299 species that span more than 400 million years of evolution and identified a clade in the genus Saturnispora that convergently evolved aerobic fermentation. Through comparative genomics and transcriptomics, we found that several glycolytic genes had higher expression and novel cis-regulatory elements in aerobically fermenting Saturnispora species. When the transcription factor required for their activation was deleted in Saturnispora dispora, the mutants had reduced glycolytic rates and increased respiration. Intriguingly, many of the upregulated genes are orthologous to duplicated glycolytic genes in S. cerevisiae. These divergent genetic mechanisms affecting the same set of genes suggest that there are strong evolutionary constraints on how aerobic fermentation can arise.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655319","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

Multifunctional roles of Brl1-Brr6 in nuclear envelope fusion during nuclear pore complex biogenesis. Brl1-Brr6在核孔复合体生物发生过程中核膜融合中的多功能作用。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-16 DOI: 10.1038/s44318-026-00718-y

Sayan Mondal, Annett Neuner, Azqa Ajmal Khan, Jlenia Vitale, Elmar Schiebel

{"title":"Multifunctional roles of Brl1-Brr6 in nuclear envelope fusion during nuclear pore complex biogenesis.","authors":"Sayan Mondal, Annett Neuner, Azqa Ajmal Khan, Jlenia Vitale, Elmar Schiebel","doi":"10.1038/s44318-026-00718-y","DOIUrl":"10.1038/s44318-026-00718-y","url":null,"abstract":"Brl1 and Brr6 are integral membrane proteins of the yeast nuclear envelope (NE) that transiently associate with nuclear pore complexes (NPCs). The exact roles of Brl1 and Brr6 during NPC assembly are unclear. Here, we demonstrate that Brr6 operates at both early and late stages of NPC assembly. Its early function is supported by amphipathic α-helix mutants, which impact nucleoporin recruitment without nuclear envelope deformation, whereas mutations in conserved cysteine residues result in NE deformation accompanied by defective NE fusion. The N-terminus of Brl1 interacts with the nucleoporin Nic96, promoting Nic96 recruitment to early assembly sites. AlphaFold predictions, the essential role of the conserved PAL motif, and the inhibition of NE fusion upon overexpression of PAL mutants together suggest that the perinuclear domains of Brl1 and Brr6 interact across the perinuclear space. Extending the length of the perinuclear-space regions of Brl1 and Brr6 causes uncontrolled NE fusion, as indicated by nuclear envelope disintegration dependent on the conserved cysteine residues. Together, Brl1 and Brr6 promote NE fusion by bridging the perinuclear space through PAL motif interactions, followed by nuclear envelope fusion and NPC insertion.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2370-2399"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208020","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

Lipopolysaccharide confinement in the bacterial outer membrane is governed by interactions within the conserved Lipid A anchor. 脂多糖在细菌外膜的限制是由保守的脂质A锚内的相互作用所控制的。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-17 DOI: 10.1038/s44318-026-00711-5

Joe Nabarro, Rosalyn M Leaman, Samuel Lenton, Leonore Mantion, Richard J Spears, Mark C Coles, Dmitri O Pushkin, Martin A Fascione, Christoph G Baumann

{"title":"Lipopolysaccharide confinement in the bacterial outer membrane is governed by interactions within the conserved Lipid A anchor.","authors":"Joe Nabarro, Rosalyn M Leaman, Samuel Lenton, Leonore Mantion, Richard J Spears, Mark C Coles, Dmitri O Pushkin, Martin A Fascione, Christoph G Baumann","doi":"10.1038/s44318-026-00711-5","DOIUrl":"10.1038/s44318-026-00711-5","url":null,"abstract":"The outer membrane of Gram-negative bacteria is an asymmetric bilayer in which lipopolysaccharide (LPS), the principal component of the outer leaflet, promotes tight packing and ordering of the membrane components that are essential for the barrier and load-bearing functions of this membrane. Lipopolysaccharide mobility is known to be restricted in the outer membrane, but this confinement and the underlying biophysical interactions responsible remain to be fully characterized. Here, we apply a bio-orthogonal strategy for in situ site-specific fluorescent labeling of LPS. Using fluorescence microscopy, we quantify LPS lateral confinement in the outer membrane of Escherichia coli and demonstrate that this confinement is independent of oligosaccharide domain structure. We show that lipopolysaccharide assembles into discrete supramolecular structures, and that restricted lateral mobility arises from a combination of divalent cation-mediated electrostatic interactions in the anionic Lipid A headgroup, and hydrophobic interactions between acyl chains within the lipid milieu. Magnesium cations exert a greater influence than calcium cations on lipopolysaccharide lateral mobility. These traits are conserved across multiple pathogenic bacterial species, irrespective of O-antigen serotype, showing that lipopolysaccharide confinement is a ubiquitous feature of Gram-negative bacteria.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2338-2369"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214906","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-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis. 膜相关外排体协调结核分枝杆菌多金属耐药。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-13 DOI: 10.1038/s44318-026-00715-1

Pierre Dupuy, Yves-Marie Boudehen, Marion Faucher, John A Buglino, Allison Fay, Sylvain Cantaloube, Yasmina Grimoire, Julien Marcoux, Florian Levet, Laetitia Bettarel, Bertille Voisin, Jérôme Rech, Jean-Yves Bouet, Olivier Saurel, Jean-Baptiste Sibarita, Michael Glickman, Claude Gutierrez, Olivier Neyrolles

{"title":"Membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis.","authors":"Pierre Dupuy, Yves-Marie Boudehen, Marion Faucher, John A Buglino, Allison Fay, Sylvain Cantaloube, Yasmina Grimoire, Julien Marcoux, Florian Levet, Laetitia Bettarel, Bertille Voisin, Jérôme Rech, Jean-Yves Bouet, Olivier Saurel, Jean-Baptiste Sibarita, Michael Glickman, Claude Gutierrez, Olivier Neyrolles","doi":"10.1038/s44318-026-00715-1","DOIUrl":"10.1038/s44318-026-00715-1","url":null,"abstract":"Bacterial pathogens must withstand metal-induced stress during infection, yet the mechanisms by which they sense and respond to toxic metal ions remain incompletely understood. Here, we uncover a previously unrecognized mechanism in Mycobacterium tuberculosis, the causative agent of tuberculosis, which assembles dynamic, membrane-associated platforms organized by PacL proteins to mediate resistance to multiple metals. The small membrane-associated proteins PacL1, PacL2, and PacL3 coordinate the clustering of P-type ATPase pumps, namely CtpC, CtpG, and CtpV, into functional complexes that we term effluxosomes. Using single-particle tracking, we reveal distinct dynamic populations, with highly mobile PacL proteins integrating into more slowly mobile effluxosomes. PacL proteins stabilize CtpC and CtpG within these assemblies, promoting cross-resistance to zinc and cadmium, with PacL1 acting as a multi-substrate metallochaperone that binds zinc, cadmium, and copper via a conserved C-terminal motif. Single-molecule-based super-resolution microscopy shows that conserved residues within the PacL transmembrane domain are essential for effluxosome assembly. Strikingly, proximity labeling reveals a broad PacL1 interaction network, suggesting that effluxosomes contribute to a wider stress adaptation program. These findings establish effluxosomes as dynamic membrane machineries that orchestrate coordinated multi-metal resistance in M. tuberculosis, opening new avenues for antimicrobial targeting.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2306-2337"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196064","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

Salt-stress-induced tomato sweetening involves an SlSnRK2.6-SlZHD8 sugar accumulation cascade triggered by root-derived abscisic acid. 盐胁迫诱导的番茄甜味涉及由根源脱落酸触发的SlSnRK2.6-SlZHD8糖积累级联。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-02 DOI: 10.1038/s44318-026-00708-0

Jinghao Xu, Zhiliang Zhang, Jin-Wei Wei, Yingfang Zhu, Dan Zhao, Tianchen Xia, Xiaoqian Liu, Chengqiang Wang, Biao Gong

{"title":"Salt-stress-induced tomato sweetening involves an SlSnRK2.6-SlZHD8 sugar accumulation cascade triggered by root-derived abscisic acid.","authors":"Jinghao Xu, Zhiliang Zhang, Jin-Wei Wei, Yingfang Zhu, Dan Zhao, Tianchen Xia, Xiaoqian Liu, Chengqiang Wang, Biao Gong","doi":"10.1038/s44318-026-00708-0","DOIUrl":"10.1038/s44318-026-00708-0","url":null,"abstract":"Crop quality arises from the interplay of genetics and environment. While moderate salt stress is known to enhance fruit sweetness, the underlying molecular mechanisms remain unclear. Using tomato (Solanum lycopersicum) as a model, this study investigates how salt stress promotes fruit sugar accumulation. Root-derived abscisic acid (ABA) transport to fruit acts as the key signal under salt stress. Elevated fruit-ABA activates the kinase SlSnRK2.6, which phosphorylates the SlZHD8 transcription factor. This phosphorylation inhibits SlZHD8 function by reducing its protein stability and DNA-binding, thereby relieving its repression of SlSUS3 and SlSWEET12 to enhance fruit-sugar accumulation. Furthermore, the SlSnRK2.6-SlZHD8-SlSWEET12 module also regulates root-sugar accumulation and confers salt tolerance. Evolutionary analysis revealed a beneficial ZHD8 haplotype, whose reduced promoter-binding affinity promotes fruit-sugar accumulation under normal conditions and enhances salt tolerance. These findings explain how stress enhances quality and highlight the potential of key mutations of ZHD8, particularly the beneficial haplotype, for breeding tomatoes with improved sugar content and salt tolerance.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2134-2156"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108379","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

Structural determinants for GPCR-mediated inhibition of TASK K2P channels by diacylglycerol and its dysfunction in disease. gpcr介导的二酰基甘油抑制TASK K2P通道的结构决定因素及其在疾病中的功能障碍。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-25 DOI: 10.1038/s44318-026-00710-6

Thibault R H Jouen-Tachoire, Peter Proks, David Seiferth, Kate Crowther, Philip C Biggin, Thomas Baukrowitz, Marcus Schewe, Stephen J Tucker

{"title":"Structural determinants for GPCR-mediated inhibition of TASK K2P channels by diacylglycerol and its dysfunction in disease.","authors":"Thibault R H Jouen-Tachoire, Peter Proks, David Seiferth, Kate Crowther, Philip C Biggin, Thomas Baukrowitz, Marcus Schewe, Stephen J Tucker","doi":"10.1038/s44318-026-00710-6","DOIUrl":"10.1038/s44318-026-00710-6","url":null,"abstract":"Two-Pore Domain K+ (K2P) channels are crucial determinants of the resting membrane potential and of cellular electrical excitability in many different cell types. TASK-1 and TASK-3 K2P channel activity is also coupled to GPCR signalling pathways via Gαq and their subsequent inhibition is via direct interaction with diacylglycerol (DAG) generated from phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis. This regulation is defective in two different neurodevelopmental disorders, but the molecular mechanisms underlying this inhibitory process and the reasons for the GPCR-insensitivity of these disease-causing mutations remain unclear. Here we show that GqPCR inhibition inversely correlates with channel open probability, and results from a state-dependent destabilisation of the open state by DAG promoting channel closure. We also identify a DAG interaction-site within a groove between the M2, M3 and M4 domains, and show the crucial role of residues within this site in mediating the inhibitory effect and defining channel sensitivity. These results not only reveal the structural and molecular mechanisms underlying GqPCR regulation of TASK channels, but also explain the pathogenic effect of a common regulatory defect linked to different K2P channelopathies.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2400-2412"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311509","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

STARD3 regulates lysosome positioning and contacts via a GSK3-controlled phosphorylation switch. STARD3通过gsk3控制的磷酸化开关调节溶酶体的定位和接触。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-25 DOI: 10.1038/s44318-026-00705-3

Julie Eichler, Corinne Wendling, Sophie Huver, Mehdi Zouiouich, Victor Hanss, Anna Cardinal, Victoria Fimbel, Catherine Birck, Alastair G McEwen, Céline Knorr, Catherine Fromental-Ramain, Maxime Boutry, Marie-Pierre Chenard, Guillaume Drin, Catherine Tomasetto, Fabien Alpy

{"title":"STARD3 regulates lysosome positioning and contacts via a GSK3-controlled phosphorylation switch.","authors":"Julie Eichler, Corinne Wendling, Sophie Huver, Mehdi Zouiouich, Victor Hanss, Anna Cardinal, Victoria Fimbel, Catherine Birck, Alastair G McEwen, Céline Knorr, Catherine Fromental-Ramain, Maxime Boutry, Marie-Pierre Chenard, Guillaume Drin, Catherine Tomasetto, Fabien Alpy","doi":"10.1038/s44318-026-00705-3","DOIUrl":"10.1038/s44318-026-00705-3","url":null,"abstract":"Membrane contact sites (MCS) are dynamic regions where the membranes of two organelles come into close apposition. MCSs play many roles in cellular homeostasis by facilitating inter-organelle lipid exchange and organelle positioning. The late endosome/lysosome (LE/Lys) cholesterol transfer protein STARD3 forms reversible contacts between LE/Lys and the endoplasmic reticulum (ER). This tether protein contains a Phospho-FFAT motif (two phenylalanines in an acidic tract) whose interaction with ER-resident VAPs (vesicle-associated membrane protein-associated proteins) is phosphorylation-dependent. In this study, we identify GSK3α and GSK3β as the kinases responsible for phosphorylating serine 209 within the Phospho-FFAT motif of STARD3. This phosphorylation event is both necessary and sufficient to activate STARD3's tethering activity, thereby promoting ER-LE/Lys contacts. Furthermore, we show that when ER-LE/Lys tethering is prevented, STARD3 triggers LE/Lys homotypic interactions, revealing an additional function for STARD3 on endosome biology. Our findings establish a direct and critical role for GSK3 in regulating MCS via STARD3 phosphorylation, and expand our understanding of the molecular basis of inter-organelle communication.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"2239-2277"},"PeriodicalIF":8.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312233","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

CaMKII nucleates an osmotic protein supercomplex to induce cellular bleb expansion. CaMKII形成一种渗透蛋白超复合体，诱导细胞泡扩张。

IF 8.3 1区生物学

EMBO Journal Pub Date : 2026-04-01 Epub Date: 2026-02-03 DOI: 10.1038/s44318-026-00703-5

Yuki Fujii, Yuji Sakai, Kenji Matsuzawa, Junichi Ikenouchi

引用次数: 0