title: Structure of myosin-1c tail bound to calmodulin provides insights into calcium-mediated conformational coupling.
abstract: Class I myosins can sense cellular mechanical forces and function as tension-sensitive anchors or transporters. How mechanical load is transduced from the membrane-binding tail to the force-generating head in myosin-1 is unknown. Here we determined the crystal structure of the entire tail of mouse myosin-1c in complex with apocalmodulin, showing that myosin-1c adopts a stable monomer conformation suited for force transduction. The lever-arm helix and the C-terminal extended PH domain of the motor are coupled by a stable post-IQ domain bound to calmodulin in a highly unusual mode. Ca(2+) binding to calmodulin induces major conformational changes in both IQ motifs and the post-IQ domain and increases flexibility of the myosin-1c tail. Our study provides a structural blueprint for the neck and tail domains of myosin-1 and expands the target binding modes of the master Ca(2+)-signal regulator calmodulin.
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Li
authors.affiliation: 1] Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. [2] Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: 1] Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. [2] Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. [3] State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D051379:Mice; D024461:Myosin Type I / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D024461:Myosin Type I; D002118:Calcium