Identification of a region in the coiled-coil domain of Smc3 that is essential for cohesin activity
| العنوان: | Identification of a region in the coiled-coil domain of Smc3 that is essential for cohesin activity |
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| المؤلفون: | Hadar Mor, Avi Matityahu, Itay Onn, Ola Orgil |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Conformational change, Saccharomyces cerevisiae Proteins, Cohesin complex, Chromosomal Proteins, Non-Histone, Protein Conformation, Cell Cycle Proteins, Saccharomyces cerevisiae, Biology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Protein Domains, Neoplasms, Genetics, medicine, Humans, Molecular Biology, Coiled coil, Mutation, Cohesin, SMC protein, Chromatin, Protein Structure, Tertiary, Cell biology, 030104 developmental biology, Chondroitin Sulfate Proteoglycans, chemistry, Sister Chromatid Exchange, Adenosine triphosphate |
| الوصف: | The cohesin complex plays an important role in sister chromatin cohesion. Cohesin's core is composed of two structural maintenance of chromosome (SMC) proteins, called Smc1 and Smc3. SMC proteins are built from a globular hinge domain, a rod-shaped domain composed of long anti-parallel coiled-coil (CC), and a second globular adenosine triphosphatase domain called the head. The functions of both head and hinge domains have been studied extensively, yet the function of the CC region remains elusive. We identified a mutation in the CC of smc3 (L217P) that disrupts the function of the protein. Cells carrying the smc3-L217P allele have a strong cohesion defect and complexes containing smc3-L217P are not loaded onto the chromosomes. However, the mutation does not affect inter-protein interactions in either the core complex or with the Scc2 loader. We show by molecular dynamics and biochemistry that wild-type Smc3 can adopt distinct conformations, and that adenosine triphosphate (ATP) induces the conformational change. The L217P mutation restricts the ability of the mutated protein to switch between the conformations. We suggest that the function of the CC is to transfer ATP binding/hydrolysis signals between the head and the hinge domains. The results provide a new insight into the mechanism of cohesin activity. |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80ee42b1e8c21c6414daeeaf8467f29c https://doi.org/10.1093/nar/gkw539 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....80ee42b1e8c21c6414daeeaf8467f29c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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