Journal of Molecular Biology最新文献_第8页

Chats and Spats of Autophagy and Innate Immune Systems 自噬与先天免疫系统的对话与争论。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-11 DOI: 10.1016/j.jmb.2025.169387

Soumya Kundu, Swati Chauhan, Kollori Dhar, Sriram Varahan, Santosh Chauhan

{"title":"Chats and Spats of Autophagy and Innate Immune Systems","authors":"Soumya Kundu, Swati Chauhan, Kollori Dhar, Sriram Varahan, Santosh Chauhan","doi":"10.1016/j.jmb.2025.169387","DOIUrl":"10.1016/j.jmb.2025.169387","url":null,"abstract":"<div><div>The innate immune system and autophagy are the two fundamental pillars of host defense. Both processes coordinate to maintain cellular homeostasis and protect from multiple threats, ranging from invading pathogens to cellular stresses. Innate immune pathways provide the first line of defense against infections and endogenous threats. They sense microbial structures called pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) released from stressed or damaged cells and mount robust inflammatory responses. Autophagy is a fundamental process that maintains cellular homeostasis by performing multiple functions, including the turnover of damaged organelles and the killing of intracellular pathogens. While initially considered independent pathways, an overwhelming number of studies suggest dynamic crosstalk between these two cell-autonomous systems. Understanding this bidirectional communication will help in developing novel therapeutic strategies targeting infectious diseases, autoimmune disorders, and other immune-related pathologies. This review focuses on the multifaceted relationship between autophagy and innate immunity.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169387"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843977","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

Contributions of Local Structural and Energetic Features of DNA to Large-scale Genomic Organization. DNA的局部结构和能量特征对大规模基因组组织的贡献。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-11 DOI: 10.1016/j.jmb.2025.169385

Wilma K Olson, Nicolas Clauvelin, Stefjord Todolli, Xiang-Jun Lu

引用次数: 0

Structural Basis of Novel Bile Acid-Based Modulators of FXR 新型胆汁酸基FXR调节剂的结构基础。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-11 DOI: 10.1016/j.jmb.2025.169383

D. Kydd-Sinclair , G.L. Packer , A.C. Weymouth-Wilson , K.A. Watson

{"title":"Structural Basis of Novel Bile Acid-Based Modulators of FXR","authors":"D. Kydd-Sinclair , G.L. Packer , A.C. Weymouth-Wilson , K.A. Watson","doi":"10.1016/j.jmb.2025.169383","DOIUrl":"10.1016/j.jmb.2025.169383","url":null,"abstract":"<div><div>Following its deorphanisation in the early 2000s, the farnesoid X receptor (FXR) attracted significant attention for regulating genes involved in bile acid, lipid and glucose metabolism and inflammation, pathways central to many liver diseases. As such, pharmaceutical efforts targeted FXR for their treatment. However, while FXR agonists, such as obeticholic acid, have been studied in clinical trials, many were associated with adverse effects arising from the promiscuity of systemic FXR activation, thus efforts to limit or selectively modulate the downstream effects of FXR are crucially important. In work here, two novel bile acid derivatives, previously identified via molecular docking and cell-based screening, were validated by X-ray crystallography and tested in LanthaScreen coactivator recruitment assays. Their effects on downstream FXR signalling were assessed <em>in vitro</em> in hepatocellular carcinoma cells, and <em>in vivo</em> in C57BL/6 mice, by RNA sequencing and RT-qPCR. The novel compounds exhibited potent and selective FXR agonist activity. Co-crystal structures of FXR LBD with both compounds, demonstrated distinctive binding modes for each, including occupancy of a receptor sub-pocket associated with allosteric activation, not observed with classic bile acids. Both compounds were up to four-fold more potent than obeticholic acid and demonstrated ligand-dependent differences in coactivator recruitment assays. <em>In vitro</em>, both compounds induced greater changes in the expression of FXR target genes, at lower doses than obeticholic acid. I<em>n vivo</em>, compound-dependent differential gene expression was observed. These findings suggest that the novel compounds may enable gene-specific FXR regulation through differential coactivator usage and hold potential to overcome the shortcomings of current bile acid drugs, thus representing promising candidates for further research.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169383"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843980","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 Topoisomerase II Mutations in Cancer: Structural Impact and Drug Response in High-grade Serous Ovarian Carcinoma. 癌症中的DNA拓扑异构酶ii突变：高级别浆液性卵巢癌的结构影响和药物反应。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-11 DOI: 10.1016/j.jmb.2025.169384

Viola Mazzoleni, Amélie Boichard, Valérie Lamour

{"title":"DNA Topoisomerase II Mutations in Cancer: Structural Impact and Drug Response in High-grade Serous Ovarian Carcinoma.","authors":"Viola Mazzoleni, Amélie Boichard, Valérie Lamour","doi":"10.1016/j.jmb.2025.169384","DOIUrl":"10.1016/j.jmb.2025.169384","url":null,"abstract":"<p><p>Topoisomerases are essential enzymes that resolve DNA topological stress during replication and transcription. In mammalian cells, the two isoforms, TOP2A and TOP2B, differ in expression profiles and functions. TOP2A is a key regulator of cell division, mainly expressed in rapidly dividing cells, such as cancer cells, and is therefore the primary target of several chemotherapeutic molecules. In contrast, TOP2B is ubiquitously expressed in both dividing and non-dividing cells and is not directly implicated in tumorigenesis. Despite their functional differences, the high homology of the two isoforms contributes to unwanted off-target effects of TOP2-directed therapies, sometimes leading to secondary cancer. Both isoforms can harbor naturally occurring or cancer-associated point mutations, which could confer altered sensitivity or resistance to chemotherapy agents. Using data from cancer genomic databases, we analyzed hotspot mutations of both isoforms found in human tumors and conducted a molecular analysis based on structural and functional data. We identified TOP2 variants in high-grade serous ovarian carcinoma, a malignancy frequently treated with TOP2-targeting agents, such as doxorubicin or etoposide. Our analysis emphasizes the importance of modeling somatic mutations to assess enzyme conformation and therapeutic response. Additionally, this review provides insights that underline the potential value of including TOP2A and TOP2B in companion diagnostic gene panels used in personalized oncology, notably in cancers where TOP2-directed agents are part of the standard therapy.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169384"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843979","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

Recurrent Acrodysostosis-Related PKA RIα Mutant Reveals a Novel Mechanism of Aberrant PKA Deactivation. 复发性肢端发育不全相关PKA RIα突变揭示了一种异常PKA失活的新机制。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-09 DOI: 10.1016/j.jmb.2025.169381

Leonardo Della Libera, Karla Martinez Pomier, Madoka Akimoto, Ganesh S Anand, Susan S Taylor, Giuseppe Melacini

{"title":"Recurrent Acrodysostosis-Related PKA RIα Mutant Reveals a Novel Mechanism of Aberrant PKA Deactivation.","authors":"Leonardo Della Libera, Karla Martinez Pomier, Madoka Akimoto, Ganesh S Anand, Susan S Taylor, Giuseppe Melacini","doi":"10.1016/j.jmb.2025.169381","DOIUrl":"10.1016/j.jmb.2025.169381","url":null,"abstract":"<p><p>Protein kinase A (PKA) is essential in converting extracellular signals into tightly regulated cellular responses controlling vital processes such as growth, development, and gene expression. Activation of PKA is controlled by the binding of cAMP to the regulatory subunit of PKA (R). Several mutations in the ubiquitous RIα isoform of R cause Acrodysostosis 1 (ACRO), a disease characterized by resistance to thyroid-stimulating and parathyroid hormones leading to severe congenital malformations. This work examines the recurrent R366X truncation ACRO mutant, which exhibits severe PKA hypoactivation due to loss of sensitivity to cAMP and the impairment of allosteric networks. The R366X RIα mutant has been previously studied via X-ray crystallography, but the crystal structure only captured the inhibited state and showed minimal difference from the wild type structure. Additionally, previous studies only examined the effects of ACRO mutants on the activation cycle of PKA (i.e. sensitivity to cAMP binding). Here we focus on the less understood signal termination cycle. We hypothesize that R366X acts by perturbing dynamic intermediates relevant to the PKA deactivation cycle, which are not fully recapitulated by static structures. To test our hypothesis, we combined low- and high-resolution approaches for probing protein-ligand binging, mutant stability, and identifying regions exhibiting aberrant allosteric behaviors. Based on our results, we propose a novel mechanism whereby R366X not only impairs physiological PKA activation but also accelerates PKA deactivation by increasing the rate of phosphodiesterase-catalyzed cAMP hydrolysis to 5'-AMP. Our studies shed new light on the current understanding of PKA dysregulation and ACRO's molecular etiology, outlining a multi-resolution experimental design which is transferable to other ACRO mutants.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169381"},"PeriodicalIF":4.5,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820272","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

Harnessing Allostery to Modulate Protein–Protein Interactions: From Function to Therapeutic Innovations 利用变构调节蛋白质-蛋白质相互作用：从功能到治疗创新。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-08 DOI: 10.1016/j.jmb.2025.169382

Sutanu Mukhopadhyay, Krishnendu Sinha, Suman Chakrabarty

{"title":"Harnessing Allostery to Modulate Protein–Protein Interactions: From Function to Therapeutic Innovations","authors":"Sutanu Mukhopadhyay, Krishnendu Sinha, Suman Chakrabarty","doi":"10.1016/j.jmb.2025.169382","DOIUrl":"10.1016/j.jmb.2025.169382","url":null,"abstract":"<div><div>Protein-protein interactions (PPIs) are ubiquitous mediators of cellular functions, and their dysregulation is central to numerous pathological conditions. Traditional drug discovery strategies targeting PPIs directly have faced considerable obstacles due to their extensive, flat, and dynamic interfaces, deemed conventionally “undruggable”. Allosteric regulation offers an alternative route, allowing modulation of these critical interactions through spatially distinct regulatory sites that can dynamically alter protein function without direct interference at the interface. Recent advances in computational methodologies, particularly enhanced molecular dynamics simulations and machine learning approaches, have significantly expanded our ability to identify and characterize cryptic allosteric sites and pathways. This perspective provides a comprehensive analysis of the evolving understanding of allosteric mechanisms in PPIs, highlights recent successes in computational identification and targeting of allosteric modulators, and outlines the challenges and opportunities in translating these insights into therapeutic strategies. Ultimately, this approach heralds a transformative potential in therapeutic interventions targeting complex biological networks.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 20","pages":"Article 169382"},"PeriodicalIF":4.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815470","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

NMR Approaches to Identify Transient Structure and Interactions of Intrinsically Disordered Dynein Intermediate Chain. 核磁共振方法识别内在无序动力蛋白中间链的瞬态结构和相互作用。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-07 DOI: 10.1016/j.jmb.2025.169380

Nikolaus M Loening, Kayla A Jara, Elisar J Barbar

{"title":"NMR Approaches to Identify Transient Structure and Interactions of Intrinsically Disordered Dynein Intermediate Chain.","authors":"Nikolaus M Loening, Kayla A Jara, Elisar J Barbar","doi":"10.1016/j.jmb.2025.169380","DOIUrl":"10.1016/j.jmb.2025.169380","url":null,"abstract":"<p><p>Nuclear magnetic resonance (NMR) spectroscopy is widely recognized for its ability to provide atomic-level resolution of structures and interactions in intrinsically disordered proteins (IDPs). However, its application is often limited when studying large proteins that contain both structured and disordered regions. This challenge arises due to the broad peaks exhibited by structured regions in such proteins, which result from local compaction and restricted motions, complicating spectral analysis. Additionally, broadening in IDP complexes caused by exchange between free and bound states and/or the large size of the bound state, further obscures NMR signals and hinders the mapping of interaction sites. Moreover, IDPs are highly sensitive to proteolytic cleavage, necessitating careful handling and optimization during expression, purification, and data collection. In this study, we demonstrate how we successfully overcame these hurdles using examples from our work on the N-terminal region of the dynein intermediate chain (IC), which contains both ɑ-helical and intrinsically disordered regions. By employing paramagnetic relaxation enhancement (PRE) NMR to probe conformational dynamics, water-amide chemical exchange to measure solvent accessibility, and saturation transfer difference (STD) NMR to map specific interactions with p150<sup>Glued</sup> and Nudel, we identified novel transient structures and interaction networks within IC. Our findings highlight the utility of these advanced NMR techniques in elucidating the dynamic behavior of IDPs and their complexes, providing valuable insights into their structural and functional roles.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169380"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811575","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

Nascent RNA Folding and RNP Assembly Revealed by Single-molecule Microscopy. 单分子显微镜显示的新生RNA折叠和RNP组装。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-07 DOI: 10.1016/j.jmb.2025.169365

Andrés Bustamante, Tucker J Carrocci, David A Nicholson, Margaret L Rodgers

{"title":"Nascent RNA Folding and RNP Assembly Revealed by Single-molecule Microscopy.","authors":"Andrés Bustamante, Tucker J Carrocci, David A Nicholson, Margaret L Rodgers","doi":"10.1016/j.jmb.2025.169365","DOIUrl":"10.1016/j.jmb.2025.169365","url":null,"abstract":"<p><p>The regulation of gene expression requires many RNA-protein complexes, or ribonucleoproteins (RNPs). Understanding the molecular mechanisms guiding the assembly of RNPs is a crucial step towards characterizing their roles in the cell. Assembly of an RNP, like the ribosomal subunits or the spliceosome, often occurs on the fly as a major RNA component is synthesized and co-transcriptionally folded. Yet, the timing of transcription, RNA folding, and association of binding partners must be tightly coordinated to ensure proper and rapid RNP assembly. Single-molecule methods have been pivotal in uncovering the ways RNAs navigate folding landscapes during transcription and how binding partners have adapted to guide - or circumnavigate - the RNA folding pathway. In this review, we discuss several single-molecule imaging techniques that have been recently developed to address key questions related to the kinetic control of RNA folding during transcription, mechanisms driving recruitment of binding partners, and functional links between the transcription and RNP machineries that underlie the mechanism of RNP assembly. Finally, we provide insight into the next steps to advance applications of single-molecule methods to further our understanding of RNP assembly mechanisms across the domains of life.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169365"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A New Approach to In Vivo Transformation of Killer T Cells. 杀伤T细胞体内转化的新途径

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-07 DOI: 10.1016/j.jmb.2025.169369

Noe Rodriguez, Christian Hofmann, Otto O Yang, William M Gelbart

{"title":"A New Approach to In Vivo Transformation of Killer T Cells.","authors":"Noe Rodriguez, Christian Hofmann, Otto O Yang, William M Gelbart","doi":"10.1016/j.jmb.2025.169369","DOIUrl":"10.1016/j.jmb.2025.169369","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy is a relatively new and powerful way of transforming T cells with receptors needed to recognize and kill diseased cells. Traditionally, it involves extraction of T cells from a patient, ex vivo transformation of them with CARs, expansion, and subsequent re-infusion into the patient. Recent developments aim to avoid this lengthy, costly patient-specific procedure by using various viral and non-viral vector particles for direct in vivo delivery of CAR-encoding genes. In this paper we highlight several fundamental connections between in vitro and in vivo aspects of this process. We discuss the proposed use of in vitro-reconstituted virus-like particles (VLPs), prepared from purified CAR-encoding mRNA and viral capsid protein, and functionalized with a T cell-targeting antibody. We compare and contrast these particles - and their use as gene vectors - with the several modalities currently employed that involve in cellulo generation of lentiviral or AAV vectors or in vitro complexation of nucleic acids with cationic polymers or lipid vesicles. We report the unique stoichiometric preciseness and thermodynamic stability of VLPs formed from anti-HIV-glycoprotein CAR-encoding mRNA and the capsid protein from a plant virus, and quantify the extent to which these monodisperse spherical VLPs are RNase resistant and lead to strong CAR expression in T cells. Further, in vitro cell-killing experiments are proposed, in which these CAR VLP-transformed T cells are mixed with HIV-infected cells, to be followed by in vivo experiments involving injection of the particles into HIV-infected humanized mice.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169369"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774473","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

Subtle Variations in a Client Protein Determine Bacterial Hsp90 Dependence 客户蛋白的细微变化决定了细菌对Hsp90的依赖性。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-07 DOI: 10.1016/j.jmb.2025.169378

Marie Corteggiani , Amine Ali Chaouche , Miha Bahun , Flora A. Honoré , Deborah Byrne , Sébastien Dementin , Mathieu E. Rebeaud , Olivier Genest

{"title":"Subtle Variations in a Client Protein Determine Bacterial Hsp90 Dependence","authors":"Marie Corteggiani , Amine Ali Chaouche , Miha Bahun , Flora A. Honoré , Deborah Byrne , Sébastien Dementin , Mathieu E. Rebeaud , Olivier Genest","doi":"10.1016/j.jmb.2025.169378","DOIUrl":"10.1016/j.jmb.2025.169378","url":null,"abstract":"<div><div>Chaperones ensure protein homeostasis and are conserved across species. The ATP-dependent chaperone Hsp90 is present from bacteria to eukaryotes, where it stabilizes and activates a wide range of substrate proteins called clients. However, what determines whether a protein depends on Hsp90 remains an open question. Here, we focused on the bacterial chaperone Hsp90 and its obligate client TilS (referred to as TilS<sub>So</sub>) in the bacterium <em>Shewanella oneidensis</em>. Although Hsp90 is indispensable in <em>S. oneidensis</em> under heat stress by protecting the essential protein TilS<sub>So</sub> from degradation by the protease HslUV, Hsp90 is dispensable in <em>Escherichia coli</em>, suggesting that <em>E. coli</em> TilS (TilS<sub>Ec</sub>) is Hsp90 independent. We therefore compared the TilS orthologs with respect to <em>in vitro</em> stability, <em>in vivo</em> degradation, and interaction with Hsp90 to identify determinants of Hsp90 dependence. We found that in contrast to TilS<sub>So</sub>, TilS<sub>Ec</sub> was more stable, was not degraded by protease in the absence of Hsp90, and did not interact with Hsp90, indicating that TilS<sub>Ec</sub> is not a client of Hsp90. Chimeras between TilS<sub>So</sub> and TilS<sub>Ec</sub> as well as directed mutagenesis revealed a region of TilS<sub>So</sub> that is key for protease degradation and Hsp90 protection. Consistent with these results, the growth of <em>S. oneidensis</em> producing TilS<sub>Ec</sub> was no longer dependent on Hsp90 under heat stress. Conversely, Hsp90 became essential for the growth of <em>E. coli</em> that produced TilS<sub>So</sub> instead of TilS<sub>Ec</sub>. Altogether, our work reveals that protein-specific features, such as stability and degradation sensitivity, can determine whether orthologous proteins require the bacterial Hsp90 chaperone <em>in vivo</em>.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169378"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811515","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