5F5P

Molecular Basis for Shroom2 Recognition by Rock1

Summary for 5F5P

• Entry DOI: 10.2210/pdb5f5p/pdb
• Related: 3THF 4L2W
• Descriptor: Protein Shroom2, Rho-associated protein kinase 1, CHLORIDE ION (3 entities in total)
• Functional Keywords: coiled-coil, complex, cytoskeleton, kinase, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 138410.09

Authors

Zalewski, J.K.,VanDemark, A.P.,Heroux, A. (deposition date: 2015-12-04, release date: 2016-10-19, Last modification date: 2024-10-23)

Primary citation

Zalewski, J.K.,Mo, J.H.,Heber, S.,Heroux, A.,Gardner, R.G.,Hildebrand, J.D.,VanDemark, A.P.
Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity.
J. Biol. Chem., 291:25364-25374, 2016

PubMed 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.

PubMed: 27758857
DOI: 10.1074/jbc.M116.738559

Experimental method

X-RAY DIFFRACTION (3.568 Å)