6B27

Crystal structure of human STAC2 Tandem SH3 Domains (296-411) in complex with a CaV1.1 II-III loop peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural insights into binding of STAC proteins to voltage-gated calcium channels.

Wong King Yuen, S.M.Campiglio, M.Tung, C.C.Flucher, B.E.Van Petegem, F.

(2017) Proc Natl Acad Sci U S A 114: E9520-E9528

  • DOI: https://doi.org/10.1073/pnas.1708852114
  • Primary Citation of Related Structures:  
    6B25, 6B26, 6B27, 6B28, 6B29

  • PubMed Abstract: 

    Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (Ca V 1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different Ca V isoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II-III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of Ca V 1.2.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, University of British Columbia, V6T 1Z3 Vancouver, BC, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SH3 and cysteine-rich domain-containing protein 2
A, B, C, D, E
A, B, C, D, E, F
120Homo sapiensMutation(s): 0 
Gene Names: STAC2
UniProt & NIH Common Fund Data Resources
Find proteins for Q6ZMT1 (Homo sapiens)
Explore Q6ZMT1 
Go to UniProtKB:  Q6ZMT1
PHAROS:  Q6ZMT1
GTEx:  ENSG00000141750 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6ZMT1
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Voltage-dependent L-type calcium channel subunit alpha-1S
G, H, I, J, K
G, H, I, J, K, L
14Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13698 (Homo sapiens)
Explore Q13698 
Go to UniProtKB:  Q13698
PHAROS:  Q13698
GTEx:  ENSG00000081248 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13698
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
M [auth A]
N [auth A]
O [auth A]
P [auth B]
Q [auth C]
M [auth A],
N [auth A],
O [auth A],
P [auth B],
Q [auth C],
R [auth D],
U [auth E],
V [auth F]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
CL
Query on CL

Download Ideal Coordinates CCD File 
S [auth E],
T [auth E]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.92α = 90
b = 114.65β = 90
c = 144.678γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
SCALEPACKdata scaling
PDB_EXTRACTdata extraction
DENZOdata reduction
REFMACphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)CanadaMOP-119608

Revision History  (Full details and data files)

  • Version 1.0: 2017-10-25
    Type: Initial release
  • Version 1.1: 2017-11-08
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Database references
  • Version 1.3: 2017-12-06
    Changes: Author supporting evidence
  • Version 1.4: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.5: 2024-03-13
    Changes: Data collection, Database references