title: Cooperative fluctuations point to the dimerization interface of p53 core domain.
abstract: Elastic network models are used for investigation of the p53 core domain functional dynamics. Global modes of motion indicate high positive correlations for residue fluctuations across the A-B interface, which are not observed at the B-C interface. Major hinge formation is observed at the A-B interface upon dimerization indicating stability of the A-B dimer. These findings imply A-B as the native dimerization interface, whereas B-C is the crystal interface. The A-B dimer exhibits an opening-closing motion about DNA, supporting the previously suggested clamp-like model of nonspecific DNA binding followed by diffusion. Monomer A has limited positive correlations with DNA, while monomer B exhibits high positive correlations with DNA in the functionally significant slow modes. Thus, monomer B might seem to maintain the stability of the dimer-DNA complex by forming the relatively fixed arm of the dimer clamp, whereas the other arm of the clamp, monomer A, might allow sliding via continuous association/dissociation mechanisms.
authors.affiliation: Department of Chemical Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Kantarci
authors.forename: Pemra
authors.initials: P
authors.lastname: Doruker
authors.forename: Turkan
authors.initials: T
authors.lastname: Haliloglu
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA