Coupling between ATP hydrolysis and protein conformational change in maltose transporter.
As the intracellular part of maltose transporter, MalK dimer utilizes the energy of ATP hydrolysis to drive protein conformational change, which then facilitates substrate transport. Free energy evaluation of the complete conformational change before and after ATP hydrolysis is helpful to elucidate the mechanism of chemical-to-mechanical energy conversion in MalK dimer, but is lacking in previous studies. In this work, we used molecular dynamics simulations to investigate the structural transition of MalK dimer among closed, semi-open and open states. We observed spontaneous structural transition from closed to open state in the ADP-bound system and partial closure of MalK dimer from the semi-open state in the ATP-bound system. Subsequently, we calculated the reaction pathways connecting the closed and open states for the ATP- and ADP-bound systems and evaluated the free energy profiles along the paths. Our results suggested that the closed state is stable in the presence of ATP but is markedly destabilized when ATP is hydrolyzed to ADP, which thus explains the coupling between ATP hydrolysis and protein conformational change of MalK dimer in thermodynamics. Proteins 2017; 85:207-220. © 2016 Wiley Periodicals, Inc.
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Xiaoying
X
Lv
Department of Bioinformatics and Biostatistics, State Key Laboratory of Microbial metabolism, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
Hao
H
Liu
Department of Bioinformatics and Biostatistics, State Key Laboratory of Microbial metabolism, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
Haifeng
H
Chen
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Haipeng
H
Gong
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
D018528:ATP-Binding Cassette Transporters; D029968:Escherichia coli Proteins; C489398:MalK protein, E coli; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate
ATP hydrolysis; MalK dimer; community analysis; conformational change; free energy calculation; reaction pathway