Conformational selection in the molten globule state of the nuclear coactivator binding domain of CBP

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Magnus Kjærgaard
  • Kaare Teilum
  • ,
  • Flemming Martin Poulsen, Biomolecular Sciences, Danmark
Native molten globules are the most folded kind of intrinsically disordered proteins. Little is known about the mechanism by which native molten globules bind to their cognate ligands to form fully folded complexes. The nuclear coactivator binding domain (NCBD) of CREB binding protein is particularly interesting in this respect as structural studies of its complexes have shown that NCBD folds into two remarkably different states depending on the ligand being ACTR or IRF-3. The ligand-free state of NCBD was characterized in order to understand the mechanism of folding upon ligand binding. Biophysical studies show that despite the molten globule nature of the domain, it contains a small cooperatively folded core. By NMR spectroscopy, we have demonstrated that the folded core of NCBD has a well ordered conformer with specific side chain packing. This conformer resembles the structure of the NCBD in complex with the protein ligand, ACTR, suggesting that ACTR binds to prefolded NCBD molecules from the ensemble of interconverting structures.
OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind107
Nummer28
Sider (fra-til)12535-40
Antal sider6
ISSN0027-8424
DOI
StatusUdgivet - 13 jul. 2010
Eksternt udgivetJa

Se relationer på Aarhus Universitet Citationsformater

ID: 70231102