Model of Abnormal Chromophore-Protein Interaction for Е181К Rhodopsin Mutation: Computer Molecular Dynamics Study
Tatyana Feldman1, 2, 3, Mikhail Ostrovsky1, 2, 3, Kholmirzo Kholmurodov*, 2, 4, Kenji Yasuoka5
Identifiers and Pagination:Year: 2012
First Page: 94
Last Page: 102
Publisher ID: TOBIOCJ-6-94
Article History:Received Date: 29/6/2012
Revision Received Date: 05/7/2012
Acceptance Date: 09/7/2012
Electronic publication date: 16/8/2012
Collection year: 2012
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
The interaction of the 11-cis-retinal chromophore with the surrounding amino acid residues in the chromophore center of the rhodopsin protein has been investigated for the Е181К mutant form using molecular dynamics simulation. A comparative analysis of the arrangement of the amino acid residues in the chromophore center has been performed for both wild (native) and mutant rhodopsins. It is shown that for the Е181К mutant rhodopsin there is no proper binding of 11-cis-retinal with the surrounding amino acid residues. The distortion of the conformation states in the mutant rhodopsin molecule takes place in both the chromophore center and cytoplasmic domain. Our simulations suggest that a stable covalent linkage of 11-cis-retinal with the protein part (viz. opsin) of the rhodopsin molecule will not form. This, on the other hand, implies that the protein’s active site in the cytoplasmic domain, which is responsible for the G-protein binding (so-called transducin), may not be completely blocked.
Based on our molecular simulation data, we discuss the possible correlation between retinitis pigmentosa pathogenesis and the structural and functional properties of the rhodopsin protein.