Weng Jingwei, Ma Jianpeng, Fan Kangnian, Wang Wenning
Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, China.
Biophys J. 2009 Mar 4;96(5):1918-30. doi: 10.1016/j.bpj.2008.11.035.
Putative metal-chelate-type ABC transporter HI1470/1 is homologous with vitamin B(12) importer BtuCD but exhibits a distinct inward-facing conformation in contrast to the outward-facing conformation of BtuCD. Normal-mode analysis of HI1470/1 reveals the intrinsic asymmetric conformational flexibility in this transporter and demonstrates that the transition from the inward-facing to the outward-facing conformation is realized through the asymmetric motion of individual subunits of the transporter. This analysis suggests that the asymmetric arrangement of the BtuC dimer in the crystal structure of the BtuCD-F complex represents an intermediate state relating HI1470/1 and BtuCD. Furthermore, a twisting motion between transmembrane domains and nucleotide-binding domains encoded in the lowest-frequency normal mode of this type of importer is found to contribute to the conformational transitions during the whole cycle of substrate transportation. A more complete translocation mechanism of the BtuCD type importer is proposed.
推定的金属螯合型ABC转运蛋白HI1470/1与维生素B12导入蛋白BtuCD同源，但与BtuCD向外的构象相反，呈现出独特的向内构象。对HI1470/1的正常模式分析揭示了该转运蛋白内在的不对称构象灵活性，并表明从向内构象到向外构象的转变是通过转运蛋白单个亚基的不对称运动实现的。该分析表明，BtuCD-F复合物晶体结构中BtuC二聚体的不对称排列代表了与HI1470/1和BtuCD相关的中间状态。此外，在这种类型导入蛋白最低频率正常模式中编码的跨膜结构域和核苷酸结合结构域之间的扭曲运动被发现有助于底物运输整个周期中的构象转变。提出了BtuCD型导入蛋白更完整的转运机制。
