Opis

• Tytuł:
  Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly
• Twórca:
  Kochanczyk, Tomasz;
  Nowakowski, Michał;
  Wojewska, Dominika;
  Kocyla, Anna;
  Ejchart, Andrzej;
  Kozminski, Wiktor;
  Krezel, Artur
• Opis:
  The binding of metal ions at the interface of protein complexes presents a unique and poorly understood mechanism of molecular assembly. A remarkable example is the Rad50 zinc hook domain, which is highly conserved and facilitates the Zn2+-mediated homodimerization of Rad50 proteins. Here, we present a detailed analysis of the structural and thermodynamic effects governing the formation and stability (logK12 = 20.74) of this evolutionarily conserved protein assembly. We have dissected the determinants of the stability contributed by the small β-hairpin of the domain surrounding the zinc binding motif and the coiled-coiled regions using peptides of various lengths from 4 to 45 amino acid residues, alanine substitutions and peptide bond-to-ester perturbations. In the studied series of peptides, an >650 000-fold increase of the formation constant of the dimeric complex arises from favorable enthalpy because of the increased acidity of the cysteine thiols in metal-free form and the structural properties of the dimer. The dependence of the enthalpy on the domain fragment length is partially compensated by the entropic penalty of domain folding, indicating enthalpy-entropy compensation. This study facilitates understanding of the metal-mediated protein-protein interactions in which the metal ion is critical for the tight association of protein subunits.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2016.11.03
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  Macmillan Publishers Limited
• Relacja: http://eprints.ibb.waw.pl/1277 ;http://www.nature.com/articles/srep36346 ;
  10.1038/srep36346
• Temat i słowa kluczowe:
  QH301 Biology
• Identyfikator: http://eprints.ibb.waw.pl/1277/2/SciRep-106.pdf ;
  Kochanczyk, Tomasz and Nowakowski, Michał and Wojewska, Dominika and Kocyla, Anna and Ejchart, Andrzej and Kozminski, Wiktor and Krezel, Artur (2016) Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly. Scientific Reports, 6 (36346). ISSN 2045-2322
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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