Conformational Selection in a Protein-Protein Interaction Revealed by Dynamic Pathway Analysis
| Autor: | Kalyan S. Chakrabarti, Roman V. Agafonov, Francesco Pontiggia, Renee Otten, Matthew K. Higgins, Gebhard F.X. Schertler, Daniel D. Oprian, Dorothee Kern |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 14, Iss 1, Pp 32-42 (2016) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 41643569 |
| DOI: | 10.1016/j.celrep.2015.12.010 |
| Popis: | 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 nuclear magnetic resonance (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. Protein dynamics in free recoverin limits the overall rate of binding. |
| Databáze: | Directory of Open Access Journals |
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