The linkage between protein folding and functional cooperativity: two sides of the same coin?
During the course of their biological function, proteins undergo different types of structural rearrangements ranging from local to large-scale conformational changes. These changes are usually triggered by their interactions with small-molecular-weight ligands or other macromolecules. Because binding interactions occur at specific sites and involve only a small number of residues, a chain of cooperative interactions is necessary for the propagation of binding signals to distal locations within the protein structure. This process requires an uneven structural distribution of protein stability and cooperativity as revealed by NMR-detected hydrogen/deuterium exchange experiments under native conditions. The distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework for functional cooperativity. In this review, the statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed.
Luque
Irene
I
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Leavitt
Stephanie A
SA
Freire
Ernesto
E
D000465:Algorithms; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006859:Hydrogen; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship; D013696:Temperature; D013816:Thermodynamics
D008024:Ligands; D011506:Proteins; D006859:Hydrogen