title: Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin.
abstract: Class III myosins (Myo3) and actin-bundling protein Espin play critical roles in regulating the development and maintenance of stereocilia in vertebrate hair cells, and their defects cause hereditary hearing impairments. Myo3 interacts with Espin1 through its tail homology I motif (THDI), however it is not clear how Myo3 specifically acts through Espin1 to regulate the actin bundle assembly and stabilization. Here we discover that Myo3 THDI contains a pair of repeat sequences capable of independently and strongly binding to the ankyrin repeats of Espin1, revealing an unexpected Myo3-mediated cross-linking mechanism of Espin1. The structures of Myo3 in complex with Espin1 not only elucidate the mechanism of the binding, but also reveal a Myo3-induced release of Espin1 auto-inhibition mechanism. We also provide evidence that Myo3-mediated cross-linking can further promote actin fiber bundling activity of Espin1.
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, United States.
authors.forename: Manmeet H
authors.initials: MH
authors.lastname: Raval
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Yao
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Deng
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Nie
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.|Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Yengo
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.|Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.|Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China.|Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D025102:Myosin Type III / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D000199:Actins; C493274:ESPN protein, human; C491723:MYO3B protein, human; D008840:Microfilament Proteins; C491724:MYO3A protein, human; D025102:Myosin Type III; D018995:Myosin Heavy Chains
keywords: Espin; actin bundles; biophysics; cell biology; myosin III; structural biology; unconventional myosin