Ligand-Free and -Bound Structures of the Binding Protein (LivJ) of the Escherichia coli ABC Leucine/Isoleucine/Valine Transport System: Trajectory and Dynamics of the Interdomain Rotation and L
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- 作者：Sergei Trakhanov ; Nand K. Vyas ; Hartmut Luecke ; David M. Kristensen ; Jianpeng Ma ; and Florante A. Quiocho
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：May 3, 2005
- 年：2005
- 卷：44
- 期：17
- 页码：6597 - 6608
- 全文大小：590K
- 年卷期：v.44,no.17(May 3, 2005)
- ISSN：1520-4995
文摘
The leucine/isoleucine/valine-binding protein (LIVBP or LivJ) serves as the primary high-affinity receptor of the Escherichia coli ABC-type transporter for the three aliphatic amino acids. Thefirst structure of LIVBP determined previously without bound ligand showed a molecule comprised oftwo domains which are far apart and bisected by a wide open, solvent-accessible cleft. Here we report thecrystal structures of another ligand-free state and three complexes with the aliphatic amino acids. In thepresent ligand-free structure, the two domains are farther apart. In the three very similar complex structures,the two domains are in close proximity, and each desolvated ligand is completely engulfed in the cleftand bound by both domains. The two different ligand-free structures, combined with those of the verysimilar ligand-bound structures, indicate the trajectory and backbone torsion angle changes of the hingesthat accompany domain closure and play crucial functional roles. The amino acids are bound by polarand nonpolar interactions, occurring predominantly in one domain. Consistent with the protein specificity,the aliphatic side chains of the ligands lie in a hydrophobic pocket fully formed following domain or cleftclosure. Comparison of the structures of LIVBP with several different binding proteins indicates nocorrelations between the magnitudes of the hinge-bending angles and the protein masses, the ligand sizes,or the number of segments connecting the two domains. Results of normal-mode analysis and moleculardynamics simulations are consistent with the trajectory and intrinsic flexibility of the interdomain hingesand the dominance of one domain in ligand binding in the open state.