the conformational transition pathways of atp-binding cassette transporter btucd revealed by targeted molecular dynamics simulation磷酸腺苷的构象转变途径盒式运输车btucd揭示了有针对性的分子动力学模拟.pdfVIP

The Conformational Transition Pathways of ATP-Binding Cassette Transporter BtuCD Revealed by Targeted Molecular Dynamics Simulation Jingwei Weng, Kangnian Fan, Wenning Wang* Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China Abstract BtuCD is a member of the ATP-binding cassette transporters in Escherichia coli that imports vitamin B12 into the cell by utilizing the energy of ATP hydrolysis. Crystal structures of BtuCD and its homologous protein HI1470/1 in various conformational states support the ‘‘alternating access’’ mechanism which proposes the conformational transitions of the substrate translocation pathway at transmembrane domain (TMD) between the outward-facing and inward-facing states. The conformational transition at TMD is assumed to couple with the movement of the cytoplasmic nucleotide-binding domains (NBDs) driven by ATP hydrolysis/binding. In this study, we performed targeted molecular dynamics (MD) simulations to explore the atomic details of the conformational transitions of BtuCD importer. The outward-facing to inward-facing (ORI) transition was found to be initiated by the conformational movement of NBDs. The subsequent reorientation of the substrate translocation pathway at TMD began with the closing of the periplasmic gate, followed by the opening of the cytoplamic gate in the last stage of the conformational transition due to the extensive hydrophobic interactions at this region, consistent with the functional requirement of unidirectional