Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity*
By Jenna K. Zalewski, Joshua H. Mo, Simone Heber, A. Héroux, Richard G. Gardner, J. Hildebrand, Andrew P. Vandemark. 2016
18 citations recorded by the source corpus.
Shroom-mediated remodeling of the actomyosin cytoskeleton is a critical driver of cellular shape and tissue morphology that underlies the development of many tissues including the neural tube, eye, intestines, and vasculature. Shroom uses a conserved SD2 domain to direct the subcellular localization of Rho-associated kinase (Rock), which in turn drives changes in the cytoskeleton and cellular morphology through its ability to phosphorylate and activate non-muscle myosin II. Here, we present the structure of the human Shroom-Rock binding module, revealing an unexpected stoichiometry for Shroom in which two Shroom SD2 domains bind independent surfaces on Rock. Mutation of interfacial residues impaired Shroom-Rock binding in vitro and resulted in altered remodeling of the cytoskeleton and loss of Shroom-mediated changes in cellular morphology. Additionally, we provide the first direct evidence that Shroom can function as a Rock activator. These data provide molecular insight into the Shroom-Rock interface and demonstrate that Shroom directly participates in regulating cytoskeletal dynamics, adding to its known role in Rock localization.
Subfields: Cell Biology, Molecular Biology
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In Molecular Biology
Citations in the corpus
- Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Model (2016, background): “That is, even conformational change happens, the Drosophila SD2 monomer would not resemble the Human SD2 monomer (shown in Fig.”