Surface dynamics in allosteric regulation of protein-protein interactions: modulation of calmodulin functions by Ca2+.
PLoS Comput Biol
; 9(4): e1003028, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23592972
Knowledge of the structural basis of protein-protein interactions (PPI) is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI. Allosteric modulators play an important role in regulating such interactions by binding at site(s) orthogonal to the complex interface and altering the protein's propensity for complex formation. In this work, we apply an approach recently developed by us for analyzing protein surfaces based on steered molecular dynamics simulation (SMD) to the study of the dynamic properties of functionally distinct conformations of a model protein, calmodulin (CaM), whose ability to interact with target proteins is regulated by the presence of the allosteric modulator Ca(2+). Calmodulin is a regulatory protein that acts as an intracellular Ca(2+) sensor to control a wide variety of cellular processes. We demonstrate that SMD analysis is capable of pinpointing CaM surfaces implicated in the recognition of both the allosteric modulator Ca(2+) and target proteins. Our analysis of changes in the dynamic properties of the CaM backbone elicited by Ca(2+) binding yielded new insights into the molecular mechanism of allosteric regulation of CaM-target interactions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calmodulina
/
Calcio
/
Mapeo de Interacción de Proteínas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
PLoS Comput Biol
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Israel
Pais de publicación:
Estados Unidos