Journal of Molecular Biology最新文献

KDBI-RP: Kinetic Data of RNA-Protein Interactions Database. KDBI-RP: rna -蛋白相互作用动力学数据数据库。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-11-01 Epub Date: 2025-07-25 DOI: 10.1016/j.jmb.2025.169357

Yunpeng He, Dongyue Hou, Yuzong Chen, Xian Zeng

{"title":"KDBI-RP: Kinetic Data of RNA-Protein Interactions Database.","authors":"Yunpeng He, Dongyue Hou, Yuzong Chen, Xian Zeng","doi":"10.1016/j.jmb.2025.169357","DOIUrl":"10.1016/j.jmb.2025.169357","url":null,"abstract":"Biomolecular interaction kinetics underpin essential cellular mechanisms, yet quantitative databases remain scarce for RNA-protein interactions (RPIs)-a critical regulatory axis in post-transcriptional control, synthetic biology, and therapeutic development. We previously established KDBI (Kinetic Data of Bio-molecular Interactions database) to catalog quantitative kinetics data across diverse biomolecular interaction types. Here, we present KDBI-RP, a dedicated extension focused on RPI kinetics, addressing the growing demand for RNA-centric kinetic research. KDBI-RP systematically integrates binding data for RNA-protein interactions, including kinetic rate constants-association (kon, 3657 entries) and dissociation (koff, 3761 entries)-supplemented by equilibrium dissociation constants (Kd, 175,932 entries). The database offers well-curated information on kinetic constants, assay conditions, literature sources, and comprehensive sequence, structural, and functional annotations for proteins, RNAs, and their complexes. KDBI-RP is freely accessible at http://www.kdbirp.aiddlab.com. We anticipate that KDBI-RP will serve as a valuable resource for the RNA biology and RNA-based medicine research communities.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169357"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726322","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 Analysis and Molecular Dynamics Simulations of Urease From Ureaplasma parvum. 细小脲原体脲酶的结构分析及分子动力学模拟。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.jmb.2025.169368

Heng Ning Wu, Junso Fujita, Yukiko Nakura, Masao Inoue, Koichiro Suzuki, Toru Ekimoto, Bingjie Yin, Yohta Fukuda, Kazuo Harada, Tsuyoshi Inoue, Mitsunori Ikeguchi, Keiichi Namba, Itaru Yanagihara

{"title":"Structural Analysis and Molecular Dynamics Simulations of Urease From Ureaplasma parvum.","authors":"Heng Ning Wu, Junso Fujita, Yukiko Nakura, Masao Inoue, Koichiro Suzuki, Toru Ekimoto, Bingjie Yin, Yohta Fukuda, Kazuo Harada, Tsuyoshi Inoue, Mitsunori Ikeguchi, Keiichi Namba, Itaru Yanagihara","doi":"10.1016/j.jmb.2025.169368","DOIUrl":"10.1016/j.jmb.2025.169368","url":null,"abstract":"Ureaplasma is one of the smallest pathogenic bacteria, generating approximately 95% of its adenosine triphosphate (ATP) solely through urease. Studies on Ureaplasma parvum, a species of Ureaplasma, have confirmed that adding urease inhibitors inhibits bacterial growth. The Km and Vmax of the urease-mediated reaction were estimated to be 4.3 ± 0.2 mM and 3,333.3 ± 38.0 μmol NH3/min/mg protein, respectively. The cryo-electron microscopy (cryo-EM) structure of Ureaplasma parvum urease (UPU) at a resolution of 2.03 Å reveals a trimer of heterotrimers comprising three proteins: UreA, UreB, and UreC. The active site is well conserved among the known ureases. However, the Vmax of UPU was higher than that of most known ureases, including those ureases derived from Sporosarcina pasteurii (SPU) and Klebsiella aerogenes (KAU) with identical oligomeric state. All-atom molecular dynamics simulations showed that the flap and UreB are more open in UPU than SPU and KAU. His-tagged wild-type recombinant UPU (WT-rUPU) revealed estimated Km and Vmax values of 4.1 ± 0.3 mM and 769.2 ± 7.4 µmol NH3/min/mg protein, respectively. Amino acid substitutions of recombinant UPUs within the flap region to SPU. Amongst the flap region variants, the Vmax of K331N variant was 48-fold lower than that of WT-rUPU. ICP-MS analysis reveals that one molecule of UPU, WT-rUPU, and K331N-rUPU contains 3.7, 0.8, and 0.1 Ni2+ atoms, respectively, suggesting that a wide-open flap of urease may contribute to delivering nickel into the enzyme, resulting in a high Vmax. Ureaplasma evolved highly efficient UPU through a few amino acid substitutions in the disorganized loop of the mobile flap region.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169368"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768237","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 Dynamics of SARS-CoV-2 NSP4 C-terminal Domain and Implications for Viral Processing. SARS-CoV-2 NSP4 c端结构域的结构动力学及其对病毒加工的影响

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-11-01 Epub Date: 2025-08-07 DOI: 10.1016/j.jmb.2025.169372

Lingshen Meng, Shangxiang Ye, Kai Pei, Chun Tang

{"title":"Structural Dynamics of SARS-CoV-2 NSP4 C-terminal Domain and Implications for Viral Processing.","authors":"Lingshen Meng, Shangxiang Ye, Kai Pei, Chun Tang","doi":"10.1016/j.jmb.2025.169372","DOIUrl":"10.1016/j.jmb.2025.169372","url":null,"abstract":"Coronaviruses, including SARS-CoV-2, pose a significant threat to global health. A critical step in viral maturation involves the proteolytic processing of viral polyproteins into functional nonstructural proteins (NSPs), with NSP4 being specifically cleaved by the main protease, NSP5, to release mature components. Through an integrative approach combining X-ray crystallography, NMR spectroscopy, and molecular dynamics simulations, we reveal that the C-terminal domain of NSP4 (NSP4-CTD) undergoes dynamic interconversion among multiple conformational states on distinct timescales. These states are characterized by variations in the position and secondary structure of the NSP4-CTD's C-terminal tail region, encompassing an undocked conformation, a docked extended conformation, and a docked helical conformation. We demonstrate that the formation of this C-terminal helix is influenced by both local sequence and overall structural context, playing a crucial role in positioning NSP4 relative to NSP5 and, consequently, modulating the efficiency of the autoprocessing event. While current antiviral therapeutic development has predominantly focused on targeting the mature NSP5 protease, our findings highlight the dynamic NSP4 C-terminal tail as a novel and promising target for antiviral intervention.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169372"},"PeriodicalIF":4.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787990","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

Slow dynamics orchestrate communication between binding sites in the condensation domain of a non-ribosomal peptide synthetase. 慢动力学协调非核糖体肽合成酶缩合域结合位点之间的通信。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-11 DOI: 10.1016/j.jmb.2025.169484

Megha N Karanth, Debajyoti De, John Kirkpatrick, Mark Jeeves, Teresa Carlomagno

{"title":"Slow dynamics orchestrate communication between binding sites in the condensation domain of a non-ribosomal peptide synthetase.","authors":"Megha N Karanth, Debajyoti De, John Kirkpatrick, Mark Jeeves, Teresa Carlomagno","doi":"10.1016/j.jmb.2025.169484","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169484","url":null,"abstract":"Non-ribosomal peptide synthetases (NRPSs) are complex molecular machineries that synthesize non-proteinaceous peptides in microorganisms. These peptides (NRPs) usually present a wide range of biological activities and are highly regarded as potential anti-cancer and anti-infective agents. Because of their chemical complexity, derivatives of NRPs with tailored pharmacological properties are difficult to synthesize chemically, which has triggered efforts to understand the functional mechanisms of NRPS systems and develop protein engineering strategies aimed at enabling enzymatic synthesis of non-natural NRPs. A fundamental reaction step of NRPS systems is the formation of peptide bonds between amino-acid-like building blocks. This reaction is catalysed by so-called condensation domains. The structures of several condensation domains and their complexes have been solved by crystallography and electron microscopy, but these structures have failed to provide the key to the design of artificial condensation domains. Here, we use NMR spectroscopy to reveal a complex network of dynamics in the condensation domain of the NRPS responsible for the synthesis of Tomaymycin and reveal how these motions mediate communication between the two substrate binding sites, providing a means to synchronize interactions for efficient catalysis. Our results underline the impact of dynamics, next to structure, on the function of enzymatic units and reinforce the need to consider conformational flexibility in the design of proteins with altered functions.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169484"},"PeriodicalIF":4.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285397","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

Molecular Insights into CLD Domain Dynamics and Toxin Recruitment of the HlyA E. coli T1SS. HlyA大肠杆菌T1SS CLD结构域动力学和毒素募集的分子研究

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-11 DOI: 10.1016/j.jmb.2025.169485

Rocco Gentile, Stephan Schott-Verdugo, Sakshi Khosa, Cigdem Günes, Michele Bonus, Jens Reiners, Sander H J Smits, Lutz Schmitt, Holger Gohlke

{"title":"Molecular Insights into CLD Domain Dynamics and Toxin Recruitment of the HlyA E. coli T1SS.","authors":"Rocco Gentile, Stephan Schott-Verdugo, Sakshi Khosa, Cigdem Günes, Michele Bonus, Jens Reiners, Sander H J Smits, Lutz Schmitt, Holger Gohlke","doi":"10.1016/j.jmb.2025.169485","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169485","url":null,"abstract":"Escherichia coli is a Gram-negative opportunistic pathogen causing nosocomial infections through the production of various virulence factors. Type 1 secretion systems (T1SS) contribute to virulence by mediating the one-step secretion of unfolded substrates into the extracellular space, bypassing the periplasm. A well-studied example is the hemolysin A (HlyA) system, which secretes HlyA toxin in an unfolded state across the inner and outer membranes. T1SS typically comprise a homodimeric ABC transporter (HlyB), a membrane fusion protein (HlyD), and the outer membrane protein TolC. Some ABC transporters in T1SS also contain N-terminal C39 peptidase or peptidase-like (CLD) domains implicated in substrate interaction or activation. Recent cryo-EM studies have resolved the inner-membrane complex as trimer of HlyB homodimers with associated HlyD protomers. However, a full structural model including TolC remains unavailable. We present the first complete structural model of the HlyA T1SS, constructed using template- and MSA-based information and validated by SAXS. Molecular dynamics simulations provide insights into the function of the CLD domains, which are partially absent from existing cryo-EM structures. These domains may modulate transport by stabilizing specific conformations of the complex. Simulations with a C-terminal fragment of HlyA indicate that toxin binding occurs in the occluded conformation of HlyB, potentially initiating substrate transport through a single HlyB protomer before transitioning to an inward-facing state. HlyA binding also induces allosteric effects on HlyD, affecting key residues involved in TolC recruitment. These results indicate how substrate recognition and transport are coupled and may support the development of antimicrobial strategies targeting the T1SS.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169485"},"PeriodicalIF":4.5,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285329","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

The symmetric structure of the antigenic loop in Type B HBV surface antigen. 乙型肝炎病毒表面抗原抗原环的对称结构。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-09 DOI: 10.1016/j.jmb.2025.169483

Weiyu Tao, Xiao He, Lei Chen

引用次数: 0

Temporal regulation of signal recognition particle during translation. 翻译过程中信号识别粒子的时间调控。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-09 DOI: 10.1016/j.jmb.2025.169482

Ruilin Qian, Radoslaw J Gora, Sowmya Chandrasekar, Shu-Ou Shan

{"title":"Temporal regulation of signal recognition particle during translation.","authors":"Ruilin Qian, Radoslaw J Gora, Sowmya Chandrasekar, Shu-Ou Shan","doi":"10.1016/j.jmb.2025.169482","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169482","url":null,"abstract":"Signal recognition particle (SRP) is a universally conserved protein targeting machine that directs newly synthesized proteins to the endoplasmic reticulum (ER). SRP recognizes signal sequences on nascent ER proteins as they emerge from the ribosome and, in response, activates interaction with the SRP receptor (SR) at the ER membrane. Early work suggested that SRP loses targeting competence as the nascent chain elongates; however, the underlying molecular mechanism remains unclear. Here we address this question using a combination of steady-state and single-molecule fluorescence spectroscopy measurements. A Förster resonance energy transfer (FRET) assay revealed increased dynamic excursions of the signal sequence from SRP on ribosomes bearing longer nascent chains, leading to a suboptimal conformation of SRP and its impaired interaction kinetics with SR. In addition, the nascent polypeptide associated complex (NAC) amplifies the effects of longer nascent chains to further exclude SRP from ER targeting. Our findings reveal the profound effects of an elongating nascent polypeptide on the conformation and activity of SRP and a key role of NAC in the temporal regulation of SRP, which together impose a limited window for cotranslational ER protein targeting during protein synthesis.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169482"},"PeriodicalIF":4.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273423","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

The interdomain loop modulates conformational dynamics for the antibiotic-resistant activity of TEM-type extended-spectrum β-lactamases. 结构域间环调节tem型宽谱β-内酰胺酶耐药活性的构象动力学。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-07 DOI: 10.1016/j.jmb.2025.169481

Tsz-Fung Wong, Pui-Kin So, Wai-Po Kong, Zhong-Ping Yao

{"title":"The interdomain loop modulates conformational dynamics for the antibiotic-resistant activity of TEM-type extended-spectrum β-lactamases.","authors":"Tsz-Fung Wong, Pui-Kin So, Wai-Po Kong, Zhong-Ping Yao","doi":"10.1016/j.jmb.2025.169481","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169481","url":null,"abstract":"Extended-spectrum β-lactamases (ESBLs) are bacteria-produced enzymes that can hydrolyze and confer extra resistance to new generation β-lactam antibiotics. TEM-type ESBLs are clinically prevalent and have caused serious health problems worldwide. TEM-type ESBLs are the evolutionary products of wild-type TEM-1 β-lactamase mainly through individual or combined mutations of G238S, E104K and M182T, but how these mutations cause conformational dynamics changes of the enzymes and how these changes correlate to their extended-spectrum antibiotic resistance remain unclear. Using hydrogen/deuterium exchange mass spectrometry integrated with molecular dynamics simulation, we revealed the significant effects of these individual or combined mutations on the conformational dynamics of the all-α-domain, α/β-domain and interdomain loop of the enzymes. Particularly, we observed different conformational dynamics changes of the interdomain loop in response to different mutations and substrate binding, which indicated the important role of the interdomain loop in modulating conformational dynamics of ESBLs for the catalytic efficiency. These new findings shed new insights into the antibiotic-resistance mechanism of TEM-type ESBLs and designing of novel inhibitors, and provide clues for the evolutionary strategy of β-lactamases and the studies of proteins with similar linking loops.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169481"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257066","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

Rising Stars: Molecular Mechanisms and Chemical Interventions of α-Synuclein Amyloid Aggregation in Parkinson's Disease. 新星：帕金森病α-突触核蛋白淀粉样蛋白聚集的分子机制和化学干预。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-07 DOI: 10.1016/j.jmb.2025.169475

Shengnan Zhang, Kaien Liu, Dan Li, Cong Liu

{"title":"Rising Stars: Molecular Mechanisms and Chemical Interventions of α-Synuclein Amyloid Aggregation in Parkinson's Disease.","authors":"Shengnan Zhang, Kaien Liu, Dan Li, Cong Liu","doi":"10.1016/j.jmb.2025.169475","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169475","url":null,"abstract":"Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by progressive neuronal loss and pathological aggregation of α-synuclein (α-syn) into amyloid fibrils, which propagate between cells and drive disease progression. Over the past decade, our laboratory has implemented an integrated strategy-combining high-resolution structural biology, molecular biophysics, biochemical and cellular analyses, chemical biology approaches, and in vivo disease models-to elucidate the molecular basis of α-syn pathology. We first determined atomic-resolution structures of full-length α-syn fibrils, revealing diverse polymorphs shaped by familial mutations and post-translational modifications, and linking conformational heterogeneity to phenotypic and pathological diversity. We further elucidated the structural basis underlying the interaction between amyloid fibril and chemical ligands, enabling the rational development of imaging probes and therapeutic modulators. In parallel, we found that the conserved acidic C-terminal region of α-syn fibrils acts as a central interface for driving pathogenic engagement with multiple receptors for neural propagation and inflammation induction, while also binding the autophagy adaptor LC3B to disrupt p62-mediated selective autophagy. Targeting this interface with small molecule inhibitors alleviates α-syn-induced toxicity in cellular models. Together, these findings provide an integrated molecular roadmap for understanding α-syn pathology and advancing precision diagnostics and targeted interventions in PD and related synucleinopathies.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169475"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257018","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

ISWI is an intrinsically dynamic nucleosome remodeler that induces large-scale histone dynamics. ISWI是一种内在动态的核小体重塑剂，可诱导大规模组蛋白动力学。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-10-07 DOI: 10.1016/j.jmb.2025.169480

Vincenzo R Lobbia, Clara L van Emmerik, María Cristina Trueba Sánchez, Johanna Ludwigsen, Felix Mueller-Planitz, Hugo van Ingen

{"title":"ISWI is an intrinsically dynamic nucleosome remodeler that induces large-scale histone dynamics.","authors":"Vincenzo R Lobbia, Clara L van Emmerik, María Cristina Trueba Sánchez, Johanna Ludwigsen, Felix Mueller-Planitz, Hugo van Ingen","doi":"10.1016/j.jmb.2025.169480","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169480","url":null,"abstract":"The chromatin remodeler ISWI plays a crucial role in the maintenance of the dynamic chromatin landscape through its ability to alter nucleosome spacing. Nucleosome remodeling by ISWI involves the translocation of DNA over the histone octamer surface, without disassembly of the nucleosome. Despite the enormous progress in the structural characterization of this process in recent years, it remains unclear to what extent conformational changes in the histone proteins play a role in remodeling. In addition, the conformation and dynamics of regulatory NTR and NegC domains within the remodeler have proven difficult to obtain. Here, we studied the conformational dynamics of fruit fly ISWI and the nucleosome-ISWI complex using solution NMR spectroscopy. We find that the NTR contains a highly dynamic DNA-binding loop and that the NegC domain is packed against ATPase lobe 2 in the free enzyme. Methyl-TROSY data indicate that the ATPase lobes and the NegC domain have substantial μs-ms motions in the free enzyme suggesting that conformational changes during the catalytic cycle are intrinsically encoded. Comparison of histone methyl-TROSY spectra upon binding of different ISWI constructs indicates that binding of a de-inhibited ISWI construct induces largest conformational changes through the histone octamer, affecting histone-DNA and histone-histone contacts. Overall, these findings refine our understanding of the conformational landscape of ISWI and provide strong support for histone plasticity during remodeling to facilitate DNA translocation, highlighting the histone octamer as an allosteric unit.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169480"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257003","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