JOURNAL OF MOLECULAR BIOLOGY分子生物学杂志
JOURNAL OF MOLECULAR BIOLOGY(英文缩写 J MOL BIOL),ISSN 0022-2836,eISSN 1089-8638,中文译名:分子生物学杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.151 | Q1 |
| 2022 | 5.600 | Q1 |
| 2023 | 4.700 | Q1 |
| 2024 | 4.500 | Q2 |
| 2025 | 4.700 | Q2 |
JOURNAL OF MOLECULAR BIOLOGY 最新收录文献
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1. Suramin and its analogues are multi-functional inhibitors of cGAS.
1. 苏拉明及其类似物是cGAS的多功能抑制剂PMID:日期:2026-09-29Upon sensing double-stranded DNA, cyclic GMP-AMP synthase (cGAS) catalyzes ATP and GTP to synthesize the cyclic dinucleotide 2',3'-cGAMP, which subsequently activates stimulator of interferon genes (STING)-mediated immune responses. Modulation of cGAS catalytic activity is crucial for treating diseases associated with the cGAS-STING pathway. Here, we found that suramin and its analogues, such as NF023, can inhibit 2',3'-cGAMP synthesis by competitively binding to cGAS. Structural analysis of the cGAS-NF023 complex reveals that NF023 binds to the active-site cleft and DNA-binding sites of cGAS, which prevents substrate access to the active site, stabilizes the activation loop in an inactive conformation and blocks cGAS-DNA binding. In addition, both suramin and NF023 disrupt cGAS-DNA phase separation, thereby potentially impairing cytosolic DNA sensing and downstream signal transduction. These findings unveil the unique mechanisms underlying cGAS inhibition by suramin and its analogues and provide the structural basis for developing cGAS inhibitors.
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2. Auto-S-fatty acylation of PKM2 regulates its tetramerization and glycolytic metabolism in cancer cells.
PMID:日期:2026-09-26Cancer cells rely on aerobic glycolysis to fuel proliferation, yet how lipid metabolism dynamically regulates glycolysis remains incompletely understood. Here, we identify pyruvate kinase M2 (PKM2) is regulated by auto-S-fatty acylation. Using bioorthogonal chemical reporters, we demonstrate that PKM2 is S-fatty acylated at a conserved cysteine residue (Cys474), preferentially incorporating C18 stearate and C16 palmitate. This modification destabilizes PKM2's active tetramer, thereby suppressing pyruvate kinase activity and altering the abundance of glycolytic intermediates. Genetic ablation of PKM2 S-fatty acylation (C474S mutant) enhances mitochondrial respiration, alters glycolytic metabolite abundance, and impairs lung cancer cell growth in vitro and in vivo. Our findings establish PKM2 auto-S‑fatty acylation as a mechanism that links fatty acid availability to glycolysis and tumor cell growth, highlighting a potential vulnerability in cancers dependent on aerobic glycolysis.
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3. MEK/ERK signaling and Bcl-2 family protein changes in influenza-infected cells with differing sulfatide levels.
PMID:日期:2026-09-23Influenza A virus (IAV) exploits host pathways to maximize progeny production. Sulfatide, a sulfated glycosphingolipid on the plasma membrane, has been implicated in enhanced influenza replication; however, the underlying host factors remain unclear. Using sulfatide-low COS7 cells, sulfatide-enriched SulCOS1 cells, and Madin-Darby canine kidney (MDCK) cells that endogenously express sulfatide, we observed higher infectious viral yields in MDCK and SulCOS1 cells than in COS7 cells, without a corresponding increase in the number of initially infected cells. IAV infection triggered time-dependent activation of mitogen-activated protein kinase (MAPK) signaling in sulfatide-enriched cells, with a prominent response in extracellular signal-regulated kinases 1 and 2 (ERK1/2). Treatment with U0126, a mitogen-activated protein kinase kinase (MEK)/ERK-pathway inhibitor, reduced viral output without a marked increase in lactate dehydrogenase (LDH) release, although ERK dependence remains unresolved. To assess mitochondrial apoptosis-related responses, we examined the pro-apoptotic BH3-only protein Bim. In sulfatide-enriched SulCOS1 cells, Bim abundance decreased during the late phase of infection, whereas Bim remained relatively stable in COS7 cells. In MDCK cells, U0126 tended to preserve Bim abundance after infection. Although caspase-3 was activated after infection, pan-caspase inhibition did not detectably reduce hemagglutination (HA) titers under the tested conditions. In addition, changes in Bcl-2 family protein abundance were observed in MDCK and SulCOS1 cells, and Bax-targeting peptides increased influenza A and B virus production in MDCK cells. Together, these data support a model in which sulfatide-associated MEK/ERK signaling, Bim-related mitochondrial checkpoint changes, and other downstream processes may collectively contribute to efficient influenza virus production.
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4. Structural Insights into MLKL-Mediated Necroptosis: Emerging Mechanisms.
PMID:日期:2026-09-23Necroptosis is a regulated form of lytic cell death that plays important roles in inflammation, host defense, and disease. Central to this pathway is mixed lineage kinase domain-like protein (MLKL), the terminal effector responsible for membrane disruption. Upon phosphorylation by receptor-interacting protein kinase 3 (RIPK3), MLKL undergoes conformational changes, oligomerizes, and translocates to cellular membranes. Despite extensive study, however, the detailed molecular mechanism by which MLKL mediates necroptosis remains incompletely understood. Multiple models have been proposed, including pore formation, cation channel activity, and higher-order or amyloid-like assemblies, yet each is supported by limited and often indirect evidence. Notably, high-resolution structures of membrane-associated, active MLKL assemblies are still lacking, hindering a unified mechanistic understanding. In addition, emerging studies suggest that membrane permeabilization and terminal membrane rupture may be mechanistically distinct processes, potentially involving additional effectors such as SIGLEC12. In this review, we summarize current structural and mechanistic insights into MLKL, including its domain architecture, activation mechanisms, and species-specific divergence. We then evaluate competing models of MLKL-mediated membrane disruption and highlight key challenges and future directions. We emphasize the need to directly visualize the active, oligomeric MLKL assemblies in the membrane-bound state and to integrate structural, biochemical, and cellular approaches for a comprehensive understanding of MLKL-mediated membrane permeabilization. Resolving these questions will be essential for understanding necroptosis and for developing therapeutic strategies targeting MLKL-mediated cell death.
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5. Molecular characterization of the orphan toxin-immunity pair Rhs2-SciX from Salmonella Typhimurium.
PMID:日期:2026-09-23The type VI secretion system (T6SS) is a dynamic nanomachine used by bacteria to compete for space and nutrients. To kill rival bacteria, the T6SS secretes toxic effector proteins directly into adjacent cells in a contact-dependent manner. Effectors have diverse biochemical functions that arise from subtle structural modifications to related enzyme folds. To protect from self-intoxication, effectors are encoded with a cognate immunity protein in effector-immunity pairs. Immunity proteins inhibit toxicity by directly binding the active site of the toxin and are as structurally diverse as their effectors. Salmonella Typhimurium has several known effectors of diverse biochemical functions, including an orphan toxin-immunity pair Rhs2-SciX. Although Rhs2 has antibacterial activity, the biochemical mechanism of Rhs2 toxicity remains unknown. Here, we take a structural approach and show that Rhs2 is related to BECR family nucleases through modeling and bacterial toxicity assays. Furthermore, we solve an X-ray crystal structure of SciX and study the solution-state properties of the immunity protein to gain insight into the binding and inhibition mechanism of Rhs2. Finally, we discover that Rhs2 binds directly to EF-Tu suggesting that Rhs2 may inhibit translation to cause cell death. Our work probes the structure and function of the orphan toxin-immunity pair Rhs2-SciX, demonstrates the biochemical diversity of Salmonella T6SS effectors, and highlights the conserved T6SS toxicity strategy of binding EF-Tu.
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6. Magnetic Tweezers Experiments Reveal Increased Mechanical Sensitivity of the F2561Y Mutant in von Willebrand Factor.
PMID:日期:2026-09-21The large glycoprotein von Willebrand factor (VWF) is essential for primary hemostasis. By sensing hydrodynamic forces in the bloodstream, VWF elongates under elevated shear, increasing its adhesiveness to platelets. This mechanosensitive behavior arises from its multidomain architecture, where distinct structural elements respond at different force scales. The stem, formed by interactions between C-domains of adjacent monomers in VWF dimers, opens at relatively low forces (∼1 pN), representing an early step in force activation. The F2561Y mutation in the C4 domain is a gain-of-function mutation associated with increased shear sensitivity and myocardial infarction, yet its effect on VWF mechanics in the physiologically relevant low-force regime remains unresolved. Here, we combine single-molecule magnetic tweezers with AFM imaging to investigate how F2561Y alters VWF stem dynamics. Magnetic tweezers measurements reveal that A2 domain unfolding remains unchanged in the mutant, whereas stem opening transitions occur at significantly lower forces compared to wild type. The midpoint force for stem opening is reduced by approximately one order of magnitude, indicating a pronounced destabilization of the compact stem conformation. AFM imaging independently confirms a higher population of open stem states in the mutant, even without applied force. Our findings demonstrate that F2561Y selectively destabilizes the VWF stem and increases its force sensitivity biasing it towards more open stem conformations, providing a direct molecular explanation for its enhanced shear responsiveness and prothrombotic phenotype. More broadly, our work establishes magnetic tweezers as a powerful approach to resolve low-force conformational equilibria in mechanosensitive proteins and to dissect the mechanical impact of disease-associated mutations.
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7. DNA Polymerase α has Cyclobutane Pyrimidine Dimer Translesion Activity that is Suppressed During Normal Replication.
PMID:日期:2026-09-21To ensure rapid and accurate DNA replication during S-phase, the cell uses DNA damage tolerance (DDT) pathways, leaving lesions to be repaired after completion of replication. One established DDT pathway is Translesion Synthesis (TLS), in which lesions are bypassed by specialized TLS Polymerases that work in conjunction with the replisome. Here we demonstrate that DNA Polymerase alpha (Pol α), the replicative primase/polymerase, can also unexpectedly replicate through a bulky lesion in vitro. We use biochemical and single-molecule fluorescence assays to characterize cyclobutane pyrimidine dimer (CPD) TLS activity of Pol α. We find that Pol α overexpression does not alter UV sensitivity in TLS-null cells. Consistent with this, we observe that Pol ε, the leading strand replicative polymerase, strongly inhibits Pol α CPD TLS activity via proofreading, even with Pol α present at much higher relative concentrations. We further show that RPA, a single-stranded DNA binding protein complex, strongly inhibits CPD TLS activity of Pol α. In contrast, Pol η, the canonical TLS Pol for pyrimidine dimers, is unaffected by Pol ε and is conversely stimulated by RPA. Finally, we demonstrate with single-molecule Fluorescence Resonance Energy Transfer (FRET) that the DNA binding cleft of Pol α must remain in the open state to accommodate a bulky CPD lesion during TLS, possibly accounting for the relatively slow kinetics of CPD bypass that we observe. The results suggest that the intrinsic bulky TLS activity of Pol α is likely suppressed at the replication fork by the replisome itself during normal replication.
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8. PrimerBac: A Searchable Database of Taxon-specific Primers for Rapid Microbial Identification.
PMID:日期:2026-09-21Species-resolved PCR detection of gut microorganisms is challenged by within-species genomic diversity and sequence conservation among related taxa. We developed PrimerBac (https://primerbac.cn), a searchable database that integrates gut-focused reference collection, RefSeq pan-genome analysis, core-orthogroup marker selection, background screening, and assembly-level ePCR evaluation. The reference intestinal resource contains 1762 species, and complete pan-genome analyses were obtained for 1179 species. PrimerBac provides 1,148,644 primer pairs for 991 prokaryotic species and 611,077 pairs for 424 genera. Broad screening of 22,207 RefSeq reference/representative assemblies yielded 68.9% sensitivity. In a non-overlapping temporal panel of 4115 post-construction assemblies, 57 of 65 evaluable targets were detected (87.7% sensitivity; 95% CI, 77.5-93.6%), with 84.0% hit-defined macro precision. PrimerBac therefore provides a searchable and systematically evaluated resource for targeted microbial identification.
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10. ZBP1 Evolution and Antagonism by Large DNA Viruses.
PMID:日期:2026-09-17ZBP1 is a nucleic acid receptor that restricts virus infection by activating an inflammatory gene response and by inducing host cell death. Left-handed Z-form nucleic acids accumulating in infected cells activate ZBP1 by binding to its N-terminal Zα domains. Signal transduction relies on the presence of RIP homotypic interaction motifs (RHIMs) that recruit the RIPK1 and RIPK3 signalling kinases to induce NF-κB activation or cell death under the forms of apoptosis or necroptosis. The expression of Zα domain proteins by poxviruses and RHIM-containing proteins by herpesviruses that antagonise ZBP1 may reflect a long-standing evolutionary interaction between ZBP1-mediated immunity and large DNA viruses. Phylogenetic analysis shows that ZBP1 likely emerged during jawed vertebrate speciation with ZBP1 orthologues first appearing in cartilaginous fish. ZBP1 is subsequently lost in entire vertebrate clades, including bony fish, scaled reptiles, birds, marsupials, and rabbits and hares, suggesting reoccurring counterselection of ZBP1-based immunity. Evidence of a ZBP1-like protein in distantly related bivalve molluscs indicates that sensing of Z-form nucleic acids coupled to RHIM-mediated signal transduction has evolved at least twice throughout the animal kingdom. Here, we study the origins, structure and function of ZBP1 and its Zα domains and RHIMs, discuss their respective roles in sensing Z-nucleic acids and signal transduction, and review ZBP1's mutually antagonistic relationship with large DNA viruses.