5f4y
From Proteopedia
Structure of the SD2 domain of Human Shroom2
Structural highlights
Function[SHRM2_HUMAN] May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). Publication Abstract from PubMedShroom-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-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 Shrm in which two Shrm 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. Structure of the Shroom-Rho kinase complex reveals a binding interface with monomeric Shroom that regulates cell morphology and stimulates kinase activity.,Zalewski JK, Mo JH, Heber S, Heroux A, Gardner RG, Hildebrand JD, VanDemark AP J Biol Chem. 2016 Oct 10. pii: jbc.M116.738559. PMID:27758857[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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