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Title: Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity

Journal Article · · Journal of Biological Chemistry
 [1];  [1];  [1];  [2];  [3];  [1];  [1]
  1. Univ. of Pittsburgh, PA (United States). Dept. of Biological Sciences
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Dept. of Biology
  3. Univ. of Washington, Seattle, WA (United States). Dept. of Pharmacology
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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 in this paper, 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. In addition, 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.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
Grant/Contract Number:
SC0012704; GM097204
OSTI ID:
1351714
Report Number(s):
BNL-113675-2017-JA
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 49; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 13 works
Citation information provided by
Web of Science

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Cited By (7)

Scoria: a Python module for manipulating 3D molecular data journal September 2017
Pyrite: A blender plugin for visualizing molecular dynamics simulations using industry-standard rendering techniques: Pyrite: Visualizing MD Simulations in Blender journal December 2017
SOCS2 Binds to and Regulates EphA2 through Multiple Mechanisms journal September 2017
Genetic and functional analysis of SHROOM1-4 in a Chinese neural tube defect cohort journal February 2018
SHROOM2 inhibits tumor metastasis through RhoA–ROCK pathway-dependent and -independent mechanisms in nasopharyngeal carcinoma journal January 2019
Folic acid modifies the shape of epithelial cells during morphogenesis via a Folr1 and MLCK dependent mechanism journal January 2019
RhoBTB1 interacts with ROCKs and inhibits invasion journal September 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Shroom
serine/threonine-protein kinase
coiled-coil
Structural Biology
RhoA
Cell Contractility
cytoskeleton
Rock
X-ray crystallography