1 Ocak 2020 Dergi makalesi Açık Erişim

Gul, Seref; Aydin, Cihan; Ozcan, Onur; Gurkan, Berke; Surme, Saliha; Baris, Ibrahim; Kavakli, Ibrahim Halil

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{
  "@context": "https://schema.org/", 
  "@id": 9225, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Dept Chem & Biol Engn, Istanbul, Turkey", 
      "name": "Gul, Seref"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Istanbul Medeniyet Univ, Dept Mol Biol & Genet, Istanbul, Turkey", 
      "name": "Aydin, Cihan"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Dept Mol Biol & Genet, Istanbul, Turkey", 
      "name": "Ozcan, Onur"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Dept Mol Biol & Genet, Istanbul, Turkey", 
      "name": "Gurkan, Berke"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Dept Mol Biol & Genet, Istanbul, Turkey", 
      "name": "Surme, Saliha"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Koc Univ, Dept Mol Biol & Genet, Istanbul, Turkey", 
      "name": "Baris, Ibrahim"
    }, 
    {
      "@type": "Person", 
      "name": "Kavakli, Ibrahim Halil"
    }
  ], 
  "datePublished": "2020-01-01", 
  "description": "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.", 
  "headline": "The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm", 
  "identifier": 9225, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm", 
  "url": "https://aperta.ulakbim.gov.tr/record/9225"
}