Zalewski, Jenna K. and Mo, Joshua H. and Heber, Simone and Heroux, Annie and Gardner, Richard G. and Hildebrand, Jeffrey D. and VanDemark, Andrew P.
(2016)
Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity.
Journal of Biological Chemistry, 291 (49).
pp. 25364-25374.
ISSN 0021-9258
Abstract
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.
Share
Citation/Export: |
|
Social Networking: |
|
Details
Metrics
Monthly Views for the past 3 years
Plum Analytics
Altmetric.com
Actions (login required)
|
View Item |