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dc.contributor.authorFas, Burcu Aykac
dc.contributor.authorTutar, Yusuf
dc.contributor.authorHaliloglu, Turkan
dc.descriptionWOS: 000322320200029en_US
dc.descriptionPubMed ID: 23874183en_US
dc.description.abstractEscherichia coli cyclic AMP Receptor Protein (CRP) undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD) simulations and Gaussian Network Model (GNM). The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra-and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.en_US
dc.description.sponsorshipTUBITAK [107T415]en_US
dc.description.sponsorshipThis work has been partially supported by TUBITAK Project No. 107T415. TH acknowledges DPT 2010K120670. TH acknowledges Betil Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.titleDynamic Fluctuations Provide the Basis of a Conformational Switch Mechanism in Apo Cyclic AMP Receptor Proteinen_US
dc.contributor.department[Fas, Burcu Aykac -- Haliloglu, Turkan] Bogazici Univ, Dept Chem Engn, Istanbul, Turkey -- [Fas, Burcu Aykac -- Haliloglu, Turkan] Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey -- [Tutar, Yusuf] Cumhuriyet Univ, Fac Med, Dept Chem, Dept Biochem, Sivas, Turkey -- [Tutar, Yusuf] Cumhuriyet Univ, Fac Med, CUTFAM Res Ctr, Sivas, Turkeyen_US
dc.contributor.authorIDAykac Fas, Burcu -- 0000-0003-3842-731Xen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US

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