{"title":"黏结蛋白的功能活性可被化学伴侣改变。","authors":"Sayali Marathe, Haripriya Chougule, Vandana Nikam, Amitabha Majumdar, Tania Bose","doi":"10.1007/s10930-025-10276-7","DOIUrl":null,"url":null,"abstract":"<div><p>The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. We have used <i>Saccharomyces cerevisiae</i> to mimic the cohesinopathy disorder Roberts syndrome with mutations (<i>eco1W216G</i>) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts’ phenotype. Molecular docking has helped us identify the possible sites on Eco1, which could possibly alter the phenotypic traits.</p></div>","PeriodicalId":793,"journal":{"name":"The Protein Journal","volume":"44 5","pages":"550 - 569"},"PeriodicalIF":1.4000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Functional Activities of Cohesin Proteins Can Be Altered by Chemical Chaperones\",\"authors\":\"Sayali Marathe, Haripriya Chougule, Vandana Nikam, Amitabha Majumdar, Tania Bose\",\"doi\":\"10.1007/s10930-025-10276-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. We have used <i>Saccharomyces cerevisiae</i> to mimic the cohesinopathy disorder Roberts syndrome with mutations (<i>eco1W216G</i>) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts’ phenotype. Molecular docking has helped us identify the possible sites on Eco1, which could possibly alter the phenotypic traits.</p></div>\",\"PeriodicalId\":793,\"journal\":{\"name\":\"The Protein Journal\",\"volume\":\"44 5\",\"pages\":\"550 - 569\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Protein Journal\",\"FirstCategoryId\":\"2\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10930-025-10276-7\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Protein Journal","FirstCategoryId":"2","ListUrlMain":"https://link.springer.com/article/10.1007/s10930-025-10276-7","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Functional Activities of Cohesin Proteins Can Be Altered by Chemical Chaperones
The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. We have used Saccharomyces cerevisiae to mimic the cohesinopathy disorder Roberts syndrome with mutations (eco1W216G) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts’ phenotype. Molecular docking has helped us identify the possible sites on Eco1, which could possibly alter the phenotypic traits.
期刊介绍:
The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.