Poster Presentation 2014 International Biophysics Congress

Insight into the selectivity of α conotoxin BuIA on the nAChR α6 subunit studied by molecular dynamics simulations (#470)

Thi Hong Tham Phan 1 2 , Myunggi Yi 1 2
  1. Center for Marine-Integrated Biomedical Technology, Pukyong National University, Busan, South Korea
  2. Department of Biomedical Engineering , Pukyong National University, Busan, South Korea

Nicotinic acetylcholine receptors (nAChRs) are members of the ligand-gated ion channel superfamily and essential in neurotransmission. A recent experimental study has identified 3 residues (Lys185, Asp187, Ile188) of α6 subunit as determinant of the selectivity on the α-conotoxin BuIA. However, the atomic detail of the structure-function relationship is still elucidated.

In this research, we have carried out molecular dynamic simulations with two systems: wild type α4β2 and mutant by 3 residues of α6 subunit (Tyr185Lys, Thr187Asp, Arg188Ile) with the toxin. The result gave information that the wild type α4β2 has lost hydrogen bond pair between Asp199-Arg188, and after mutation the hydrogen bond pair was replaced by new one between Lys185-Asp187. The average appearance ratio was 74.82% for Asp199-Arg188 and 32.86% for Lys185-Asp187, respectively, through the whole simulation time. Thus, loop C of mutant α4β2 lost rigid form, became more open and flexible form than the wild type. In the mutant simulation, we also recognized the reduced distance between toxin and subunits in the binding site that constructed by the interface between two adjacent subunits: principal and complementary subunits. After mutation, the distance between the center of the toxin and the principal subunit decreased from 25.32 Å to 23.71 Å, and distance between the center of toxin and complementary subunits decreased from 16.31 Å to 14.76 Å. These conformational changes have conferred the toxin selectivity of the α6 subunit.