Journal of Biological Chemistry最新文献

{"title":"Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signalling.","authors":"Fangyu Li,Shun Cui","doi":"10.1016/j.jbc.2025.108500","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108500","url":null,"abstract":"The complement system plays an important role in bone growth during physiological development and skeletal homeostasis. However, the specific impact of the complement C3a receptor (C3aR) on age-related bone loss remains unclear. In this study, we found that C3aR expression increased with age and was the same as that of the senescent molecules p53, p21 and p16 in control mice. Knockdown of C3aR reduced the expression of senescence markers and significantly ameliorated bone senescence. Notably, C3aR knockdown in mice effectively reversed age-induced bone loss, which was characterized by an increase in the number of osteoblasts and a decrease in the number of osteoclasts. In an in vitro model of D-gal-induced senescence, increased expression of C3aR correlated with increased expression of senescence markers such as p53, p21, and p16. Treatment with a C3aR antagonist (JR14a) successfully attenuated the expression of these markers of cellular senescence and reduced the proportion of late apoptotic cells. Mechanistically, JR14a treatment mitigated D-gal-mediated inhibition of osteoblastic differentiation in preosteoblasts through activation of the YAP1/β-catenin signalling pathway. In D-gal-induced aging mouse model, treatment with JR14a ameliorates bone microarchitecture and bone loss. In summary, these studies revealed a role for C3aR in regulating bone homeostasis, suggesting that targeting C3aR may be a promising therapeutic strategy for the treatment of age-related osteoporosis.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"75 1","pages":"108500"},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824784","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}

{"title":"α-Synuclein interacts directly with AP2 and regulates its binding to synaptic membranes.","authors":"Karina J Vargas,Jaqulin N Wallace,Ian Mooney,David J Owen,Jennifer R Morgan","doi":"10.1016/j.jbc.2025.108502","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108502","url":null,"abstract":"α-Synuclein mutation and aggregation are associated with several neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. It is expressed in the presynaptic compartment where it regulates clathrin mediated synaptic vesicle endocytosis. We have shown that α-synuclein regulates clathrin lattice size and curvature in vitro. However, the molecular mechanism by which this occurs remains unknown. Here, we show a strong colocalization between the heterotetrametric clathrin adaptor protein-2 (AP2) and α-synuclein at presynapses. Moreover, we report a direct biochemical interaction between the AP2 core domain and the C-terminal domain of α-synuclein. We further show that α-synuclein binds to isolated synaptic membranes in an ATP-dependent manner, similar to AP2 and the monomeric adaptor protein, 180 KDa (AP180), suggesting that α-synuclein, AP2 and AP180 share a common synaptic membrane binding pathway. In contrast, other endocytic proteins, such as clathrin heavy chain and the large GTPase dynamin-1 bind to synaptic membranes independently of ATP. After immunodepleting α-synuclein, we observed a specific reduction in AP2 binding to synaptic membranes, indicating that α-synuclein interaction with AP2 is necessary to maintain normal levels of AP2 on synaptic membranes. These findings demonstrate that α-synuclein plays a critical role in stabilizing AP2 on synaptic membranes, an event which is required for initiation of clathrin-mediated synaptic vesicle endocytosis.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"38 1","pages":"108502"},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824825","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}

{"title":"Mechanism and kinetics of turnover inhibitors of nicotinamide N-methyl transferase in vitro and in vivo.","authors":"T Akerud,C De Fusco,P Brandt,F Bergström,P Johansson,M Ek,U Börjesson,A Johansson,J Danielsson,M Bauer,B Arnaud,M Castaldo,M Strömstedt,B Rosengren,F Jansen,L Fredlund","doi":"10.1016/j.jbc.2025.108492","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108492","url":null,"abstract":"Nicotinamide N-methyl transferase (NNMT) is involved in the regulation of cellular nicotinamide adenine dinucleotide (NAD) and S-Adenosyl-L-methionine (SAM) levels and has been implicated in a range of human diseases. Herein, we show that a class of NNMT inhibitors; analogues of the natural substrate nicotinamide (NAM) are turned over by the enzyme and that the methylated product is a potent inhibitor of the enzyme. The product inhibitor is, however, charged and has modest cellular potency. Utilizing this on-target biotransformation combines the cell permeability of the substrate with the high potency of the product that results in highly efficient inhibition in vivo. First we studied the structure-activity-relationship for both substrates and methylated products and solved structures using X-ray crystallography of representative inhibitors. Then we designed a new surface biosensor method to understand the structure-kinetic-relationship for the inhibitors. We were able to quantify the substrate binding kinetics to NNMT-SAM, catalysis rate and rate of product release from NNMT-SAH in a single experiment. This is to our knowledge the first time an enzyme surface biosensor has been used to study and quantify catalysis in detail. Finally, by monitoring plasma concentrations of turnover inhibitor substrate, product and the endogenous product, 1-Methyl nicotinamide (1-MNA), in the rat, we show that the turnover inhibitor mechanism of action is relevant in vivo.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"1 1","pages":"108492"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822456","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}

{"title":"Molecular interactions of glucocorticoid and mineralocorticoid receptors define novel transcription and biological functions.","authors":"Tatsuya Sueyoshi,Maria G Petrillo,Christine M Jewell,Carl D Bortner,Lalith Perera,Xiaojiang Xu,Felipe I Aguayo,David Diaz-Jimenez,Anastasia G Robinson,Molly E Cook,Robert H Oakley,John A Cidlowski","doi":"10.1016/j.jbc.2025.108488","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108488","url":null,"abstract":"Glucocorticoids are primary stress hormones necessary for life that function to maintain homeostasis. These hormones and their synthetic derivatives are widely used in the clinic to combat disease but are limited by development of resistance and by severe side effects. Understanding how glucocorticoids signal is crucial for developing safer and more effective glucocorticoids. Mechanistically glucocorticoid ligands induce glucocorticoid receptor (GR) homodimerization and regulation of gene expression. Here we show that GR and mineralocorticoid receptor (MR) form molecular complexes with distinct transcriptional responses that alter the biological roles of GR. MR inhibited GR interaction with genomic DNA and diminished glucocorticoid-regulated gene expression as well as suppressed cell apoptosis induced by GR signaling. Provocatively, multiple therapeutic glucocorticoids differentially induced the GR-MR interaction revealing unknown drug effects that are exploitable for fine-tuning glucocorticoid drug treatments. Molecular modeling of the GR-MR complex predicted an interaction interface residing in the LBD of both GR and MR. Mutation of a key amino acid in the interface of GR compromised GR - MR interaction without affecting GR activity in a gene reporter assay. Overall, our findings uncovered unique crosstalk mechanisms between distinct nuclear receptors providing a novel mechanism of diversity in the action of glucocorticoids that may contribute to context-dependent GR signaling in human health and disease.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"108 1","pages":"108488"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822467","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}

{"title":"ADP ribosylation factor-like GTPase 6-interacting protein 5 (Arl6IP5) is an ER membrane-shaping protein that modulates ER-phagy.","authors":"Yasunori Yamamoto,Toshiaki Sakisaka","doi":"10.1016/j.jbc.2025.108493","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108493","url":null,"abstract":"The endoplasmic reticulum (ER) is the membrane-bound organelle characterized by the reticular network of tubules. It is well established that the ER tubules are shaped by ER membrane proteins containing the conserved reticulon-homology domain (RHD). Membrane shaping by the RHD-containing proteins is also involved in regulation of ER-phagy, selective autophagy of the ER. However, it remains unclear whether there exists ER membrane-shaping proteins other than the RHD-containing proteins. In this study, we characterize Arl6IP5, an ER membrane protein containing the conserved PRA1 domain, as an ER membrane-shaping protein. Upon overexpression, Arl6IP5 induces the extensive network of the ER tubules, and constricts the ER membrane as judged by exclusion of a luminal ER enzyme from the ER tubules. The membrane constriction by Arl6IP5 allows the cells to maintain the tubular ER network in the absence of microtubules. siRNA-mediated knockdown of Arl6IP5 impairs the ER morphology, and the phenotype of the Arl6IP5 knockdown cells is rescued by exogenous expression of Arl6IP1, an RHD-containing protein. Furthermore, exogenous expression of Arl6IP5 rescues the phenotype of Arl6IP1 knockdown cells, and the PRA1 domain is sufficient to rescue it. Upon disruption of the possible short hairpin structures of the PRA1 domain, Arl6IP5 abolishes membrane constriction. The siRNA-mediated knockdown of Arl6IP5 impairs flux of the ER-phagy mediated by FAM134B. These results indicate that Arl6IP5 acts as an ER membrane-shaping protein involved in regulation of ER-phagy, implying that the PRA1 domain may serve as a general membrane-shaping unit other than the RHD.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"16 1","pages":"108493"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822533","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}

{"title":"HKDC1 promotes colorectal cancer progression by regulating RCOR1 expression to activate the Wnt/β-catenin pathway, enhancing proliferation, migration, and epithelial-mesenchymal transition (EMT).","authors":"Shansong Huang,Qiang Pang,Yufeng Zhang,Jiaqing Cao","doi":"10.1016/j.jbc.2025.108478","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108478","url":null,"abstract":"HKDC1 (Hexokinase Domain Containing 1) has been identified as an oncogenic factor in various malignancies. The role and mechanisms of HKDC1 in colorectal cancer (CRC) are not well known. This study aims to investigate the expression pattern of HKDC1 in CRC and its role in tumor growth, migration, glycolysis, and EMT, as well as to elucidate the underlying molecular mechanisms. We analyzed HKDC1 expression across multiple cancers using TIMER2.0 and TCGA databases, and assessed its prognostic value with Kaplan-Meier survival analysis. HKDC1 expression in CRC tissues was validated by Western blotting (WB), immunohistochemistry (IHC), and qRT-PCR, and its correlation with patient prognosis was examined. Functional studies involving HKDC1 knockdown and overexpression were conducted to examine its impact on CRC cell proliferation, migration, cell cycle, apoptosis, and EMT. Co-immunoprecipitation (Co-IP), Immunofluorescence (IF) and mass spectrometry identified HKDC1's interaction with RCOR1, revealing HKDC1's regulation of the Wnt/β-catenin pathway through RCOR1 to promote CRC progression. HKDC1 exhibited high expression levels in CRC tissues and cells, correlating with poor prognosis in CRC patients. Functional assays revealed that HKDC1 knockdown significantly inhibited CRC cell proliferation and migration, induced G1 phase cell cycle arrest, and promoted apoptosis, whereas HKDC1 overexpression produced the opposite effects. HKDC1 modulated EMT and increased glycolysis through the Wnt/β-catenin signaling pathway. HKDC1 knockdown inhibited CRC tumor growth in vivo, whereas its overexpression promoted tumor progression. HKDC1 interacted with RCOR1 to upregulate its expression, activating the Wnt/β-catenin pathway and promoting CRC cell proliferation, migration, and EMT. This study is the first to demonstrate that HKDC1 enhances CRC proliferation, migration, glycolysis, and EMT by modulating RCOR1 and activating the Wnt/β-catenin pathway. HKDC1 could be a therapeutic target and prognostic marker in CRC, providing new insights for personalized treatment.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"107 1","pages":"108478"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822541","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}

{"title":"GLUT2/SLC2A2 is a bi-directional urate transporter.","authors":"Yu Toyoda,Ryuichiro Shigesawa,Tony R Merriman,Hirotaka Matsuo,Tappei Takada","doi":"10.1016/j.jbc.2025.108485","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108485","url":null,"abstract":"Recent genetic studies showed an association between solute carrier 2A2 (SLC2A2), which encodes glucose transporter 2 (GLUT2), and serum urate concentrations; however, urate transport activity of GLUT2 has not been studied contrary to its function as a sugar transporter. Here, we hypothesized that GLUT2 acts also as a urate transporter, which led us to conduct cell-based functional analyses using HEK-derived 293A cells. We found that radiolabeled [8-14C]-urate was incorporated into GLUT2-expressing cells more compared to control cells and this elevated cellular activity was almost completely inhibited by GLUT2 inhibitors, demonstrating that GLUT2 is a urate transporter. Regarding the concentration dependence of GLUT2-mediated urate transport, no saturable properties were observed within an experimentally achievable range (0-500 μM), suggesting that GLUT2 mediates the robust transport of urate. Moreover, the GLUT2-mediated urate transport was not inhibited by 10 mM glucose; GLUT2-mediated sugar transport was hardly affected by 500 μM urate. As these concentrations of urate and glucose were relevant to their maximum levels in healthy humans, our results suggest that GLUT2 maintains its urate transport ability under physiological conditions, Furthermore, using a cell-based urate efflux assay system, we successfully demonstrated that urate secretion was accelerated in GLUT2-expressing cells than in control cells. Therefore, GLUT2 may also function as a urate exporter. The present study revealed that GLUT2 is a bi-directional urate transporter. Our findings contribute to a deeper understanding of urate-handling systems in the body. To elucidate the physiological role of GLUT2 as a urate transporter, further studies are required.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"39 1","pages":"108485"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822468","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}

{"title":"Melanin Concentrating Hormone-sleep pressure loop regulates melanin degradation through both autophagic degradation and lysosomal hydrolysis in zebrafish.","authors":"Qingquan Guo,Yudong Zhang,Jianhua Zhang,Xiaoyu Tian,Yawen Zhou,Yaxin Wang,Mingjie He,Lu Chen,Jiaqi Zeng,Chuanjin Tang,Qiuru Li,Zhenming He,Bingji Ma,Chenyang Jiang,Haishan Zhao","doi":"10.1016/j.jbc.2025.108486","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108486","url":null,"abstract":"Melanin-Concentrating Hormone (MCH) is a cyclic peptide initially isolated from salmon and later found to be conserved in mammals. It plays a role in regulating melanin changes and rhythmic behaviors such as sleep and feeding, though its relationship with these processes is not fully understood. Our preliminary research revealed significant differences in melanin degradation in zebrafish under varying light conditions, suggesting a link to MCH. This study aims to explore MCH's role in lighting-induced changes in rhythmic behavior patterns and melanin of zebrafish. Using the zebrafish model, we evaluated MCH expression under different lighting conditions and analyzed the effects of arousal-promoting and sleep-inducing agents. We also investigated the impact of exogenous MCH and its inhibitors on melanin degradation, behavioral changes, and differences in MCH expression to uncover potential regulatory relationships between MCH, sleep pressure, and melanin. In-depth research using flow cytometry, AO staining, Lyso-Tracker Red staining, and RT-qPCR analysis of autophagy- and apoptosis-related genes showed that melanin degradation regulation depends on MCH expression levels. Sleep pressure can intervene in MCH's effects, forming a regulatory loop to jointly regulates melanin degradation. The influence of the MCH-sleep pressure loop on melanin degradation is closely tied to autophagic and lysosomal pathways. Our findings reveal a mutually regulatory loop in zebrafish between MCH and sleep pressure, affecting melanin degradation through these pathways.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"6 1","pages":"108486"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822452","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}

{"title":"A strategy for liver selective NRF2 induction via cytochrome P450 activated prodrugs with low activity in hypoxia.","authors":"Mei Ying Ng,Thilo Hagen","doi":"10.1016/j.jbc.2025.108487","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108487","url":null,"abstract":"Activation of the transcription factor NRF2 has been shown to be a promising therapeutic approach in the treatment of hepatosteatosis. NRF2 is believed to exert beneficial effects by upregulating cellular oxidative defense mechanisms and inhibiting inflammation. However, a major concern associated with long-term treatment with NRF2 activators are drug side effects, including the promotion of tumorigenesis. Many NRF2 activators function by forming cysteine adducts with KEAP1, which normally mediates the ubiquitination and degradation of NRF2. In this study we identified NRF2 activator prodrugs of 4-methylcatechol and tert-butylhydroquinone. These prodrugs are converted into their active metabolites in a liver selective, cytochrome P450 dependent manner and function by inhibiting KEAP1, resulting in NRF2 activation. Unexpectedly, we also found that a number of NRF2 activating compounds, including 4-methylcatechol and tert-butylhydroquinone, show a markedly lower activity under hypoxic conditions compared to normoxia. Our findings suggest that the lower activity of these NRF2 inducers is a consequence of less potent cysteine adduct formation with KEAP1. The lower activity of NRF2 inducing compounds in hypoxia may limit tumor promoting effects of NRF2 induction. Our study provides an important proof of concept that it is possible to selectively activate NRF2 in the liver for the treatment of hepatosteatosis while avoiding tumorigenic effects as well as side effects of NRF2 activation in other tissues.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"16 1","pages":"108487"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822457","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}

{"title":"The ribonucleoprotein hnRNPA1 mediates RNA and DNA telomeric G-quadruplexes through an RGG-rich region.","authors":"Sangeetha Balasubramanian,Irawati Roy,Rajeswari Appadurai,Anand Srivastava","doi":"10.1016/j.jbc.2025.108491","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108491","url":null,"abstract":"hnRNPA1, a protein from the heterogeneous-nuclear ribonucleoprotein family, mediates cellular processes such as RNA metabolism and DNA telomere maintenance. Besides the folded RNA recognition motifs, hnRNPA1 has a ∼135 amino-acids long low-complexity domain (LCD) consisting of an RGG-rich region and a prion-like domain (PrLD). Biochemical data suggest that the RGG-rich region modulates recognition of G-quadruplexes (GQs) in the telomeric repeats. Here, we utilize an in-house developed replica exchange technique (REHT) to generate the heterogeneous conformational ensemble of hnRNPA1-RGG and explore its functional significance in telomere maintenance. Single chain statistics and abundance of structural motifs, as well as consistency with experimentally reported structural data suggest faithful recapitulation of local interactions. We also introduce a protocol to generate functionally significant IDP-nucleic acid complex structures that corroborate well with the experimental knowledge of their binding. We find that RGG-box preferentially binds to the grooves and loops of GQs providing specificity towards certain GQ structures with its sequence and secondary structures. Turn-like structures expose Phe and promote stacking with the G-tetrads, while Tyr and Asn residues form essential hydrogen bonds and electrostatic interactions. Several of these residues were also identified as important by the earlier reported HSQC chemical shift data. Our binding and simulation studies also reveal that a minor population of the RGG-box can perturb telomeric GQs structure, which likely expedites the unfolding activities of hnRNPA1-UP1 at the telomeric end.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"60 1","pages":"108491"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822459","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}