How Does a Registry Change in Dynein鈥檚 Coiled-Coil Stalk Drive Binding of Dynein to Microtubules?

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• 作者：Junghyun Choi ; Hahnbeom Park ; Chaok Seok
• 刊名：Biochemistry
• 出版年：2011
• 出版时间：September 6, 2011
• 年：2011
• 卷：50
• 期：35
• 页码：7629-7636
• 全文大小：437K
• 年卷期：v.50,no.35(September 6, 2011)
• ISSN：1520-4995

文摘

Dynein is a motor protein that transports cellular cargo along the microtubule (MT) by consuming ATP. Dynein鈥檚 microtubule-binding domain (MTBD) is separated from the ATP-binding core by a 15 nm stalk that consists of two 伪-helices forming an antiparallel coiled coil. It was previously suggested that the coiled-coil stalk creates a registry shift to modulate its binding affinity for MT. A crystal structure of the low-affinity form of MTBD was determined, but that of the high-affinity form with the registry shift is not yet available. In this study, we obtained an all-atom model structure for the high-affinity form of MTBD bound to MT by an anisotropic network model, protein鈥損rotein docking, and molecular dynamics simulations. We observe that the magnitude of the coiled-coil helix sliding is dramatically reduced near the two prolines that form the stalk鈥揗TBD boundary and subsequently transformed to cyclic movements of MTBD helices, leading to formation of a new salt bridge with MT at the binding interface. The proposed mechanism explains the roles of highly conserved residues such as the two prolines at the stalk鈥揗TBD boundary, the nonpolar tryptophan and proline residues near the binding interface, and the electropositive residues forming salt bridges with MT.