title: How does a registry change in dynein's coiled-coil stalk drive binding of dynein to microtubules?
abstract: Dynein is a motor protein that transports cellular cargo along the microtubule (MT) by consuming ATP. Dynein's microtubule-binding domain (MTBD) is separated from the ATP-binding core by a ~15 nm stalk that consists of two α-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-protein 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-MTBD 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-MTBD boundary, the nonpolar tryptophan and proline residues near the binding interface, and the electropositive residues forming salt bridges with MT.
authors.affiliation: Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Choi
authors.forename: Hahnbeom
authors.initials: H
authors.lastname: Park
authors.forename: Chaok
authors.initials: C
authors.lastname: Seok
mesh_terms: D000818:Animals; D016880:Anisotropy; D001665:Binding Sites / Q000502:physiology; D018360:Crystallography, X-Ray; D004398:Dyneins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016963:Thermus thermophilus / Q000201:enzymology
chemical_list: C533386:Dynlt1b protein, mouse; D004398:Dyneins