5F5P

Molecular Basis for Shroom2 Recognition by Rock1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.271 
  • R-Value Observed: 0.273 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

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

Zalewski, J.K.Mo, J.H.Heber, S.Heroux, A.Gardner, R.G.Hildebrand, J.D.VanDemark, A.P.

(2016) J Biol Chem 291: 25364-25374

  • DOI: https://doi.org/10.1074/jbc.M116.738559
  • Primary Citation of Related Structures:  
    5F4Y, 5F5P

  • 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.


  • Organizational Affiliation

    From the Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Shroom2
A, B, G, H
217Homo sapiensMutation(s): 0 
Gene Names: SHROOM2APXL
UniProt & NIH Common Fund Data Resources
Find proteins for Q13796 (Homo sapiens)
Explore Q13796 
Go to UniProtKB:  Q13796
PHAROS:  Q13796
GTEx:  ENSG00000146950 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13796
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Rho-associated protein kinase 1
C, D, E, F
86Homo sapiensMutation(s): 0 
Gene Names: ROCK1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q13464 (Homo sapiens)
Explore Q13464 
Go to UniProtKB:  Q13464
PHAROS:  Q13464
GTEx:  ENSG00000067900 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13464
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.57 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.271 
  • R-Value Observed: 0.273 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.587α = 90
b = 133.795β = 90
c = 135.871γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Cootmodel building
HKL-2000data scaling
PHENIXphasing
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesGM097204

Revision History  (Full details and data files)

  • Version 1.0: 2016-10-19
    Type: Initial release
  • Version 1.1: 2016-11-02
    Changes: Derived calculations
  • Version 1.2: 2016-12-14
    Changes: Database references
  • Version 1.3: 2017-09-20
    Changes: Author supporting evidence
  • Version 1.4: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Refinement description