Journal of Molecular Biology最新文献

Distinct allosteric links between SNARE motif and transmembrane domain differentially regulate the function of Ca²⁺ sensors. SNARE基序和跨膜结构域之间的不同变构联系差异调节Ca2+传感器的功能。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-06 DOI: 10.1016/j.jmb.2026.170090

Kinjal Sanghrajka, Sougata Majumdar, Sruthilaya Dayanandan, Ravindra Venkatramani, Debasis Das

引用次数: 0

DAXX maintains chromosomal stability by keeping methylation levels at specific repetitive elements. DAXX通过保持特定重复元件的甲基化水平来维持染色体的稳定性。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-06 DOI: 10.1016/j.jmb.2026.170091

Karla Torres-Arciga, Erick Navarro-Delgado, Samuel Ruiz-Pérez, Michelle Castillo-González, Clementina Castro, Miguel Santibánez-Andrade, Luis A Herrera, Rodrigo González-Barrios

{"title":"DAXX maintains chromosomal stability by keeping methylation levels at specific repetitive elements.","authors":"Karla Torres-Arciga, Erick Navarro-Delgado, Samuel Ruiz-Pérez, Michelle Castillo-González, Clementina Castro, Miguel Santibánez-Andrade, Luis A Herrera, Rodrigo González-Barrios","doi":"10.1016/j.jmb.2026.170091","DOIUrl":"https://doi.org/10.1016/j.jmb.2026.170091","url":null,"abstract":"Chromosomal instability (CIN), a common hallmark in most solid cancers, is characterized by structural and numerical errors during cell division. Maintenance and repression of constitutive heterochromatin, including regions like telomeres and pericentromeres, as well as repetitive elements (RE), is a critical step in preventing CIN. The histone chaperone DAXX, together with other epigenetic factors, helps preserve repression at these loci by depositing histone H3.3 and supporting histone repressive marks and DNA methylation. In the present study, we knocked down DAXX in the CIN-stable colorectal cancer cell line HCT116. We observed an increase in micronuclei and loss of DNA methylation at specific heterochromatic regions, which in turn led to the abnormal expression of repetitive elements such as the LRT7Y subfamily, normally active only during development. These findings highlight the role of DAXX in maintaining genomic stability by regulating heterochromatin and silencing specific repetitive elements.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170091"},"PeriodicalIF":4.7,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149356972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Conserved RNA architecture organizes Mg²⁺-mediated RNA assemblies into functionally competent structural states. 保守的RNA结构组织Mg2+介导的RNA组装成功能胜任的结构状态。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-03 DOI: 10.1016/j.jmb.2026.170085

Jing-Hong Tu, Ying-Chi Wang, Chiaolong Hsiao

引用次数: 0

Cancer-associated SF3B1 mutation inhibits apoptosis via circATP9B. 癌症相关SF3B1突变通过circATP9B抑制细胞凋亡。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-03 DOI: 10.1016/j.jmb.2026.170089

Rui Qian, Xuanxuan Sun, Ting Yang, Yueru Shi, Peipei An, Xin Hu, Youzhong Wan

引用次数: 0

Post-transcriptional regulation of FGF signaling: insights from musculoskeletal system. FGF信号的转录后调控：来自肌肉骨骼系统的见解。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-03 DOI: 10.1016/j.jmb.2026.170087

Laurène Alicia Lecaudey, Zeinab Ghasemishahrestani, Vahid Saqagandomabadi, Jørgen Wesche, Ehsan Pashay Ahi

{"title":"Post-transcriptional regulation of FGF signaling: insights from musculoskeletal system.","authors":"Laurène Alicia Lecaudey, Zeinab Ghasemishahrestani, Vahid Saqagandomabadi, Jørgen Wesche, Ehsan Pashay Ahi","doi":"10.1016/j.jmb.2026.170087","DOIUrl":"https://doi.org/10.1016/j.jmb.2026.170087","url":null,"abstract":"Fibroblast growth factor (FGF) signaling plays a pivotal role in the development, maintenance, and regeneration of musculoskeletal tissues. While its transcriptional regulation has been extensively characterized, accumulating evidence indicates that FGF activity is also modulated by a diverse array of post-transcriptional mechanisms. In this review, microRNAs, long non-coding RNAs, alternative splicing, and RNA modifications are examined as key regulators of FGF ligands and receptors across bone, cartilage, muscle, and tooth. RNA-binding proteins are also discussed as regulators of FGF transcript stability and translation. The effects of these RNA-based mechanisms on FGF ligand and receptor abundance, isoform production, and signaling responsiveness are compared, and a pathway-specific RNA regulome is proposed as an organizing framework to integrate these mechanisms across musculoskeletal tissues. This approach also distinguishes directly demonstrated RNA-FGF interactions from indirect associations with connected signaling pathways. The therapeutic implications of targeting post-transcriptional nodes, particularly through non-coding RNAs and epitranscriptomic marks, are discussed in the context of musculoskeletal disease and regeneration, highlighting promising avenues for future musculoskeletal interventions.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170087"},"PeriodicalIF":4.7,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

DNA Analyser: An Interactive Web Server for Integrated Prediction of Local Non-B DNA Structures in Genomic Sequences. DNA分析器：用于基因组序列中局部非b DNA结构集成预测的交互式web服务器。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-02 DOI: 10.1016/j.jmb.2026.170084

Václav Brázda, Michal Petrovič, Jiří Šťastný, Jean-Louis Mergny

{"title":"DNA Analyser: An Interactive Web Server for Integrated Prediction of Local Non-B DNA Structures in Genomic Sequences.","authors":"Václav Brázda, Michal Petrovič, Jiří Šťastný, Jean-Louis Mergny","doi":"10.1016/j.jmb.2026.170084","DOIUrl":"10.1016/j.jmb.2026.170084","url":null,"abstract":"Background: Local non-B DNA structures and R-loops are associated with genome regulation and stability. CpX islands and p53 response elements provide complementary sequence annotations. Exploring these features often requires separate tools and repeated sequence submission.Main findings: DNA Analyser web server integrates G4Hunter, G4Killer, R-loop Tracker, Z-DNA Hunter, pretrained Z-DNABERT models running on CPUs, CpX Hunter and a p53-binding predictor. Palindrome analyser is linked as a separate companion server. Inputs include plain-text or FASTA upload, pasted sequences, multiple-sequence workflows and NCBI retrieval. Outputs include analysis settings, sortable regions, interactive graphics and module-specific exports. Guest and registered users have access to the same analytical functions.Biological relevance: A shared sequence workspace supports examination of structural propensity, nucleotide composition and potential regulatory elements. Predictions identify candidates for further investigation; they do not demonstrate structure formation or biological function in vivo.Significance: Integrated access reduces repeated sequence handling and helps researchers explore complementary features of the same genomic region. DNA Analyser is freely accessible through HTTPS without identity registration at https://bioinformatics.ibp.cz/#/.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170084"},"PeriodicalIF":4.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 B⁰AT1 substrate recognition and complex assembly. B0AT1底物识别及复合物组装的结构机制。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-11-02 DOI: 10.1016/j.jmb.2026.170086

Clara N Pedersen, Mads E Christensen, Tomas Heger, Dheeraj Prakaash, Syma Khalid, Azadeh Shahsavar, Poul Nissen, Charlott Stock

{"title":"Structural mechanisms of B0AT1 substrate recognition and complex assembly.","authors":"Clara N Pedersen, Mads E Christensen, Tomas Heger, Dheeraj Prakaash, Syma Khalid, Azadeh Shahsavar, Poul Nissen, Charlott Stock","doi":"10.1016/j.jmb.2026.170086","DOIUrl":"https://doi.org/10.1016/j.jmb.2026.170086","url":null,"abstract":"Amino acid transporters are essential for maintaining cellular amino acid homeostasis. The broad-specificity neutral amino acid transporter B0AT1 is predominantly expressed in the intestine and kidney, where it mediates the uptake and reuptake of neutral amino acids with varying affinities. Proper plasma-membrane localization of B0AT1 requires dimerization with angiotensin-converting enzyme 2 (ACE2) in the intestine or collectrin in the kidney. Structural information is available for apo and substrate-bound B0AT1-ACE2 complexes, but how B0AT1 interacts with different accessory proteins and recognizes smaller substrates remains enigmatic. Here, we compare cryo-EM structures of B0AT1 in complex with ACE2 or collectrin in substrate-free states, and bound to alanine, leucine or tryptophan. The complexes display only minor differences in accessory-protein binding through a conserved interaction surface. Substrate recognition follows a canonical architecture observed for other SLC6 family transporters, with subtle adaptations that potentially account for the different affinities of the three amino acids. Notably, we resolve several cholesterol molecules surrounding the transporter, highlighting a potential regulatory role of the membrane environment that we address by molecular dynamics simulations.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170086"},"PeriodicalIF":4.7,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

KinomeX: A Source-Linked, Evidence-Traceable Atlas of the Human Kinome. KinomeX：一个来源链接，证据可追溯的人类基因组图谱。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-10-29 DOI: 10.1016/j.jmb.2026.170083

Nikolay V Dokholyan

{"title":"KinomeX: A Source-Linked, Evidence-Traceable Atlas of the Human Kinome.","authors":"Nikolay V Dokholyan","doi":"10.1016/j.jmb.2026.170083","DOIUrl":"10.1016/j.jmb.2026.170083","url":null,"abstract":"Protein kinase data originate from sources with different identifiers, definitions, and evidence models. KinomeX (https://kinomex.dokhlab.org) is an online platform that aligns the human protein kinase list from KinHub with reviewed entries from UniProtKB/Swiss-Prot and links each record to source-specific evidence. The catalog includes 678 protein entries: 522 KinHub core entries with 536 kinase-domain rows, and 156 reviewed UniProt entries labeled with the Kinase keyword (KW-0418), mostly phosphorylating lipids, nucleotides, sugars, or small molecules. Kinase profiles integrate reviewed annotations, 10,043 experimental structures, AlphaFold models, 1,021,421 ligand bioactivity records, 36,396 tissue-expression data from GTEx, 63,649 ClinVar variants, and live STRING connections. Missing records are marked as unavailable. We developed the Pharmaceutical Development Interest Score (PDIS), which combines citation, clinical-trial, structural, and chemical data with adjustable component weights. These rankings are consistent across numerous weightings (median Spearman ρ = 0.955) and better reflect Pharos target development levels than citation counts alone. Examples highlight 93 under-cited but structurally and chemically accessible kinases and 47 CNS-specific kinases, with evidence on structure, chemistry, and variants. KinomeX enables evidence review and hypothesis formation, using PDIS to indicate documented development efforts rather than biological significance.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170083"},"PeriodicalIF":4.7,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

HuKSA: A Machine-Learning-Based Framework for Predicting Human Kinome Selectivity and Polypharmacology. HuKSA：一个基于机器学习的预测人类基因组选择性和多药理学的框架。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-10-22 DOI: 10.1016/j.jmb.2026.170075

Mohammad Umar Saeed, Arunabh Choudhury, Yash Mathur, Md Imtaiyaz Hassan

{"title":"HuKSA: A Machine-Learning-Based Framework for Predicting Human Kinome Selectivity and Polypharmacology.","authors":"Mohammad Umar Saeed, Arunabh Choudhury, Yash Mathur, Md Imtaiyaz Hassan","doi":"10.1016/j.jmb.2026.170075","DOIUrl":"10.1016/j.jmb.2026.170075","url":null,"abstract":"Off-target polypharmacology across the conserved kinase ATP pocket can limit the safety and efficacy of kinase-directed compounds. HuKSA is a transparent ligand-based framework that predicts kinase targets and estimates measured-kinome selectivity from a SMILES string while exposing the reference activities behind each estimate. The method compares ECFP4 fingerprints by Tanimoto similarity and applies five-neighbour, similarity-weighted read-across to an atlas of 794 compounds with measurements spanning 464 kinases. Selectivity is summarized by the S-score, the fraction of measured kinases with pActivity above 6. In this sparse matrix, a Gini coefficient calculated after padding unmeasured kinases closely tracked assay coverage, whereas the measured-panel S-score showed weak assay-count dependence. Nevertheless, S-scores remain conditional on which kinases were assayed and on the mixture of IC50, Ki and Kd measurements. In 125 atlas-excluded KLIFS and PKIDB inhibitors, an annotated target ranked first for 19.2% of compounds and within the top 10 for 55.2%. Top-10 recovery was 83.3% among compounds in the high structural-support band, but these bands are empirical similarity descriptors, not calibrated probabilities. Internal leave-one-compound-out validation gave a pooled target-activity ROC-AUC of 0.83 and S-score prediction RMSE of 0.123. Scaffold and similarity-exclusion analyses defined the applicability domain, indicating strongest performance for queries supported by close measured analogues. By displaying measured neighbours, target-specific support counts, and prediction coverage, HuKSA enables users to inspect target and selectivity hypotheses before experimental testing and follow-up biochemical validation. The publicly accessible online Streamlit web server is available at https://huksalab-tool.hf.space.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170075"},"PeriodicalIF":4.7,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

HandMol at MolecularWebXR.org: Immersive, Multiuser Visualization and Interactive Modeling with Natural Interactions, on the Web Across a Wide Range of Devices. HandMol在MolecularWebXR.org：沉浸式，多用户可视化和自然交互的交互式建模，在各种设备的网络上。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-10-13 DOI: 10.1016/j.jmb.2026.170067

Fabio Cortes Rodriguez, Lucien F Krapp, Fernando Augusto Teixeira Pinto Meireles, Giulio Tesei, Matteo Dal Peraro, Luciano A Abriata

{"title":"HandMol at MolecularWebXR.org: Immersive, Multiuser Visualization and Interactive Modeling with Natural Interactions, on the Web Across a Wide Range of Devices.","authors":"Fabio Cortes Rodriguez, Lucien F Krapp, Fernando Augusto Teixeira Pinto Meireles, Giulio Tesei, Matteo Dal Peraro, Luciano A Abriata","doi":"10.1016/j.jmb.2026.170067","DOIUrl":"10.1016/j.jmb.2026.170067","url":null,"abstract":"Understanding and manipulating the 3D structure and dynamics of molecular systems is central to all molecular sciences including structural biology. MolecularWebXR's new HandMol module provides a browser-based, multiuser environment for immersive molecular visualization and interactive modeling across all modern devices. Leveraging the WebXR standard, HandMol requires no installation, allowing users to seamlessly access shared virtual rooms from VR/AR headsets, mobile devices, or computers. HandMol enables natural interaction through hand tracking, allowing users to query atom information by pointing or to manipulate structures using bare-hand gestures. Real-time physics feedback is provided via integrated engines, including ANI-2x for small molecules, AMBER14 for atomistic biomolecular systems, and CALVADOS coarse-grained models. We demonstrate HandMol's utility through 3D-difficult tasks like ligand (un)docking, driving conformational changes, and preparing starting poses for simulations. This globally accessible platform facilitates scientific discussion, hypothesis testing, and immersive education by bridging high-performance molecular dynamics with intuitive, natural control in a collaborative virtual space. Resource link:https://molecularwebxr.org/. Direct link to HandMol:https://molecularwebxr.org/create.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"170067"},"PeriodicalIF":4.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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