Conformational Dynamics and Protein-Substrate Interaction of ABC Transporter BtuCD at the Occluded State Revealed by Molecular Dynamics Simulations
Conformational Dynamics and Protein-Substrate Interaction of ABC Transporter BtuCD at the Occluded State Revealed by Molecular Dynamics Simulations
复制标题
分子动力学模拟揭示了 ABC 转运蛋白 BtuCD 在封闭状态下的构象动力学和蛋白质-底物相互作用
DOI：
10.1021/acs.biochem.6b00386
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Wang Wenning
中科院分区：
文献类型：
--
作者：
Pan Chao;Weng Jingwei;Wang Wenning
ATP-binding cassette (ABC) transporters are ubiquitous in all three kingdoms of life and are implicated in many clinically relevant physiological processes. They couple the energy released by ATP hydrolysis to facilitate substrate translocation across cell membranes. The crystal structures of type II ABC importers have revealed their unique transmembrane domain architecture consisting of 10 transmembrane helices and their structurally conserved nucleotide-binding domains among all ABC transporters. However, molecular details of the interactions between the importers and their substrate remain largely elusive. Taking vitamin B12importer BtuCD as an exemplar of type II importers, we investigated the dynamics of its occluded state and the detailed protein–substrate interactions using molecular dynamics simulation. Our trajectories show that the importer accommodates the substrate through a nonspecific binding mode as the substrate undergoes evident vertical and tilt motions inside the translocation cavity. Extensive hydrogen bond and hydrophobic interactions were observed between the substrate and the importer; however, most of these interactions are weak, with <38% occurrence. The presence of substrate leads to enlargement of the translocation cavity, especially at its cytoplasmic end, which may activate cytoplasmic regions and probably facilitate the transportation. The perturbations caused by periplasmic binding protein and nucleotides were also investigated. The study provides deeper insight into the translocation mechanism of BtuCD.
