Inherent flexibility and protein function: The open/closed conformational transition in the N-terminal domain of calmodulin

The key to understand a protein's function often lies in its conformational dynamics. We develop a coarse-grained variational model to investigate the interplay between structural transitions, conformational flexibility, and function of the N-terminal calmodulin domain (nCaM). In this model, tw...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of chemical physics Vol. 128; no. 20; p. 205104
Main Authors: Tripathi, Swarnendu, Portman, John J
Format: Journal Article
Language:English
Published: United States 28.05.2008
Subjects:
Binding Sites
Calcium - metabolism
Calmodulin - chemistry
Calmodulin - metabolism
Kinetics
Methionine
Microcomputers
Models, Molecular
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Thermodynamics
Time Factors
ISSN:1089-7690, 1089-7690
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The key to understand a protein's function often lies in its conformational dynamics. We develop a coarse-grained variational model to investigate the interplay between structural transitions, conformational flexibility, and function of the N-terminal calmodulin domain (nCaM). In this model, two energy basins corresponding to the "closed" apo conformation and "open" holo conformation of nCaM are coupled by a uniform interpolation parameter. The resulting detailed transition route from our model is largely consistent with the recently proposed EFbeta-scaffold mechanism in EF-hand family proteins. We find that the N-terminal parts of the calcium binding loops shows higher flexibility than the C-terminal parts which form this EFbeta-scaffold structure. The structural transition of binding loops I and II are compared in detail. Our model predicts that binding loop II, with higher flexibility and earlier structural change than binding loop I, dominates the open/closed conformational transition in nCaM.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1089-7690
1089-7690
DOI:10.1063/1.2928634