an allosteric mechanism inferred from molecular dynamics simulations on phospholamban pentamer in lipid membranes从分子动力学模拟变构机制推测受五聚物在脂质膜.pdfVIP

An Allosteric Mechanism Inferred from Molecular Dynamics Simulations on Phospholamban Pentamer in Lipid Membranes Peng Lian1,2, Dong-Qing Wei1,4*, Jing-Fang Wang2,3*, Kuo-Chen Chou4 1 College of Life Science and Biotechnology and Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai, China, 2 Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, 3 Shanghai Center for Bioinformation and Technology, Shanghai, China, 4 Gordon Life Science Institute, San Diego, California, United States of America Abstract Phospholamban functions as a regulator of Ca2+ concentration of cardiac muscle cells by triggering the bioactivity of sarcoplasmic reticulum Ca2+-ATPase. In order to understand its dynamic mechanism in the environment of bilayer surroundings, we performed long time-scale molecular dynamic simulations based on the high-resolution NMR structure of phospholamban pentamer. It was observed from the molecular dynamics trajectory analyses that the conformational transitions between the ‘‘bellflower’’ and ‘‘pinwheel’’ modes were detected for phospholamban. Particularly, the two modes became quite similar to each other after phospholamban was phosphorylated at Ser16. Based on these findings, an allosteric mechanism was proposed to elucidate the dynamic process of phospholamban interacting with Ca2+-ATPase. Citation: Lian P, Wei D-Q, Wang J-F, Chou K-C (2011) An Allosteric Mechanism Inferred from Molecular Dynamics Simulations on Phospholamban Pentamer in Lipid Membranes. PLoS ONE 6(4): e18587. doi:10.1371/journal.pone.0018587 Editor: Darren R. Flower, Aston University, United Kingdom Received August 28, 2010; Accepted March 10, 2011; Published April 15, 2011 Copyright: 2011 Lian et al. T