Conformational transition pathway in the allosteric process of calcium-induced recoverin: molecular dynamics simulations.

Abstract

Recoverin is an important neuronal calcium sensor (NCS) protein, which have been implicated in a wide range of Ca(2+) signaling events in neurons and photoreceptors. To characterize the conformational transition of recoverin from the myristoyl sequestered state to the extrusion state, a series of conventional molecular dynamics (CMD) and targeted molecular dynamics (TMD) simulations were performed. The 36.8 ns long CMD and TMD simulations on recoverin revealed a reliably conformational transition pathway, which can be viewed as a sequential two-stage process. A very important mechanistic conclusion from the present TMD simulations is that the hydrophobic and hydrophilic interactions modulate the allostery cooperatively in the conformational transition pathway. In the first stage, three salt-bridges broken between Lys-84 and Gly-124, between Lys-5 and Glu-103 and between Gly-16 and Lys-97 are major components to destabilize the structure of state T and trigger the swivel of the N- and C-terminal domains. In the second stage, the rupture of H-bond Phe-56-O(...)H(O)-Thr-21 leads to the two helices of EF-1 apart from each other, destabilizing the hydrophobic interactions of the myristoyl group with its environment, whereas the making of H-bond Leu-108-O(...)H(O)-Ser-72 helps the interfacial domain maintain its structural integrity during the course of the myristoyl extrusion. The molecular dynamics simulations results are beneficial to understanding the mechanism of how and why NCS proteins make progress in the photo-signal transduction processes. Further experimental and theoretical studies are still very desirable.

• Authors: Ji-Lai Li, Cai-Yun Geng, Yuxiang Bu, Xu-Ri Huang, Chia-Chung Sun
• Journal: Journal of computational chemistry (J Comput Chem) Vol. 30 Issue 7 Pg. 1135-45 (May 2009) ISSN: 1096-987X [Electronic] United States
• PMID: 18942727 (Publication Type: Journal Article)
• Copyright: 2008 Wiley Periodicals, Inc.

Chemical References

• Recoverin
• Calcium

Topics

• Allosteric Regulation (drug effects)
• Calcium (chemistry, pharmacology)
• Computer Simulation
• Hydrogen Bonding
• Hydrophobic and Hydrophilic Interactions
• Models, Chemical
• Models, Molecular
• Protein Conformation (drug effects)
• Recoverin (chemistry, metabolism)
• Time Factors