Cooperative fluctuations point to the dimerization interface of p53 core domain


Kantarci N., Doruker P., HALİLOĞLU T.

Biophysical Journal, cilt.91, sa.2, ss.421-432, 2006 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 91 Sayı: 2
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1529/biophysj.106.077800
  • Dergi Adı: Biophysical Journal
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.421-432
  • Boğaziçi Üniversitesi Adresli: Evet

Özet

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. © 2006 by the Biophysical Society.