1 Ocak 2020 Dergi makalesi Açık Erişim

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

DataCite XML

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/9225</identifier>
  <creators>
    <creator>
      <creatorName>Gul, Seref</creatorName>
      <givenName>Seref</givenName>
      <familyName>Gul</familyName>
      <affiliation>Koc Univ, Dept Chem &amp; Biol Engn, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Aydin, Cihan</creatorName>
      <givenName>Cihan</givenName>
      <familyName>Aydin</familyName>
      <affiliation>Istanbul Medeniyet Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Ozcan, Onur</creatorName>
      <givenName>Onur</givenName>
      <familyName>Ozcan</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Gurkan, Berke</creatorName>
      <givenName>Berke</givenName>
      <familyName>Gurkan</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Surme, Saliha</creatorName>
      <givenName>Saliha</givenName>
      <familyName>Surme</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Baris, Ibrahim</creatorName>
      <givenName>Ibrahim</givenName>
      <familyName>Baris</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Kavakli, Ibrahim Halil</creatorName>
      <givenName>Ibrahim Halil</givenName>
      <familyName>Kavakli</familyName>
    </creator>
  </creators>
  <titles>
    <title>The Arg-293 Of Cryptochrome1 Is Responsible For The Allosteric Regulation Of Clock-Cry1 Binding In Circadian Rhythm</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/9225</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1074/jbc.RA120.014333</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="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.</description>
  </descriptions>
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