Thermodynamic aspects of coupled binding and folding of an intrinsically disordered protein: a computational alanine scanning study.
We have performed computational alanine scanning to gain insight into thermodynamic aspects of coupled folding and binding of the phosphorylated kinase-inducible activation domain (pKID) of CREB, and intrinsically disorder protein (IDP), to KIX. Residues of pKID directly involved in nativelike interactions at the interface were found to steeply lower their contribution to the free energy of binding. The results suggest that, with a steep lowering of the free energy of binding, it is ensured that pKID has full control of binding specificity, is not trapped in a non-native conformational state, has full plasticity for folding, and forms a thermodynamically stable complex with KIX without compromising binding kinetics.
Espinoza-Fonseca
L Michel
LM
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA. mef@ddt.biochem.umn.edu
D000409:Alanine / Q000378:metabolism*; D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D010770:Phosphotransferases / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics
D017362:Cyclic AMP Response Element-Binding Protein; D010770:Phosphotransferases; D000409:Alanine