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Ligand‐induced dimer formation of calmodulin
Author(s) -
Zhang Yong,
Tan Hongwei,
Jia Zongchao,
Chen Guangju
Publication year - 2008
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.895
Subject(s) - calmodulin , dimer , chemistry , ligand (biochemistry) , biophysics , d dimer , biochemistry , receptor , biology , enzyme , medicine , organic chemistry
Calmodulin (CaM) can bind to numerous proteins in several interaction modes. Recently a new mode of interaction was discovered, in which two CaM molecules form an X‐shaped dimer and two binding sites to trap the CaM‐binding domain (CBD) of calcineurin subunit A. However, the X‐shaped CaM dimer alone without ligand has not been observed. We performed molecular dynamics (MD) simulations and used MM_PBSA approach to investigate the properties of this new binding mode using ligand‐bound and ‐free dimer systems. MD trajectories show that two peptides of CBD play a critical role in stabilizing the X‐shaped conformation of the CaM dimer which would otherwise be unstable, leading to dimer disassembly in the absence of the ligands. Furthermore, we have analyzed the interaction free energy of the complex by MM‐PBSA method and provide further evidence to demonstrate that the CBD peptide ligands are responsible for the stabilization of the dimer. Comparing this new binding mode with the classical one represented by CaM in complex with smooth muscle myosin light chain kinase, we conclude that this new binding mode isinduced by the CBD of calcineurin subunit A. Our results explain the fact that the X‐shaped CaM dimer structure has never been observed in the absence of ligands. Copyright © 2008 John Wiley & Sons, Ltd.