Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis
Molecular recognition plays a central role in biology, and protein dynamics has been acknowledged to be important in this process. However, it is highly debated whether conformational changes happen before ligand binding to produce a binding-competent state (conformational selection) or are caused in response to ligand binding (induced fit). Proposals for both mechanisms in protein/protein recognition have been primarily based on structural arguments. However, the distinction between them is a question of the probabilities of going via these two opposing pathways. Here we present a direct demonstration of exclusive conformational selection in protein/protein recognition by measuring the flux for rhodopsin kinase binding to its regulator recoverin, an important molecular recognition in the vision system. Using NMR spectroscopy, stopped-flow kinetics and isothermal titration calorimetry we show that recoverin populates a minor conformation in solution that exposes a hydrophobic binding pocket responsible for binding rhodopsin kinase. Lastly, protein dynamics in free recoverin limits the overall rate of binding.
- Research Organization:
- Brandeis Univ., Waltham, MA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- FG02-05ER15699
- OSTI ID:
- 1394844
- Alternate ID(s):
- OSTI ID: 1239247
- Journal Information:
- Cell Reports, Journal Name: Cell Reports Vol. 14 Journal Issue: 1; ISSN 2211-1247
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- Netherlands
- Language:
- English
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