dc.contributor.author | Surme, Saliha | |
dc.contributor.author | Baris, Ibrahim | |
dc.contributor.author | Kavakli, Ibrahim Halil | |
dc.contributor.author | Gul, Şeref | |
dc.contributor.author | AYDIN, CİHAN | |
dc.contributor.author | Ozcan, Onur | |
dc.contributor.author | Gurkan, Berke | |
dc.date.accessioned | 2021-12-10T10:43:42Z | |
dc.date.available | 2021-12-10T10:43:42Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Gul Ş., AYDIN C., Ozcan O., Gurkan B., Surme S., Baris I., Kavakli I. H. , "The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm", JOURNAL OF BIOLOGICAL CHEMISTRY, cilt.295, sa.50, ss.17187-17199, 2020 | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.other | av_507640f7-235e-4c8f-8366-2035b4fc7ab1 | |
dc.identifier.other | vv_1032021 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12627/170447 | |
dc.identifier.uri | https://doi.org/10.1074/jbc.ra120.014333 | |
dc.description.abstract | Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box-driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1(-/-)Cry2(-/-) double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm. | |
dc.language.iso | eng | |
dc.subject | Aging | |
dc.subject | BİYOKİMYA VE MOLEKÜLER BİYOLOJİ | |
dc.subject | Moleküler Biyoloji ve Genetik | |
dc.subject | Yaşam Bilimleri (LIFE) | |
dc.subject | Yaşam Bilimleri | |
dc.subject | Moleküler Biyoloji ve Genetik | |
dc.subject | Sitogenetik | |
dc.subject | Temel Bilimler | |
dc.subject | Biochemistry, Genetics and Molecular Biology (miscellaneous) | |
dc.subject | Clinical Biochemistry | |
dc.subject | Cancer Research | |
dc.subject | Molecular Biology | |
dc.subject | Drug Discovery | |
dc.subject | General Biochemistry, Genetics and Molecular Biology | |
dc.subject | Biochemistry | |
dc.subject | Structural Biology | |
dc.subject | Life Sciences | |
dc.title | The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm | |
dc.type | Makale | |
dc.relation.journal | JOURNAL OF BIOLOGICAL CHEMISTRY | |
dc.contributor.department | Koç Üniversitesi , Fen Bilimleri Enstitüsü , Kimya ve Biyoloji Mühendisliği | |
dc.identifier.volume | 295 | |
dc.identifier.issue | 50 | |
dc.identifier.startpage | 17187 | |
dc.identifier.endpage | 17199 | |
dc.contributor.firstauthorID | 2536722 | |