1M27

Crystal structure of SAP/FynSH3/SLAM ternary complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

SAP couples Fyn to SLAM immune receptors.

Chan, B.Lanyi, A.Song, H.K.Griesbach, J.Simarro-Grande, M.Poy, F.Howie, D.Sumegi, J.Terhorst, C.Eck, M.J.

(2003) Nat Cell Biol 5: 155-160

  • DOI: https://doi.org/10.1038/ncb920
  • Primary Citation of Related Structures:  
    1M27

  • PubMed Abstract: 

    SAP (SLAM-associated protein) is a small lymphocyte-specific signalling molecule that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP). Consistent with its single src homology 2 (SH2) domain architecture and unusually high affinity for SLAM (also called CD150), SAP has been suggested to function by blocking binding of SHP-2 or other SH2-containing signalling proteins to SLAM receptors. Additionally, SAP has recently been shown to be required for recruitment and activation of the Src-family kinase FynT after SLAM ligation. This signalling 'adaptor' function has been difficult to conceptualize, because unlike typical SH2-adaptor proteins, SAP contains only a single SH2 domain and lacks other recognized protein interaction domains or motifs. Here, we show that the SAP SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM. The crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex reveals that SAP binds the FynT SH3 domain through a surface-surface interaction that does not involve canonical SH3 or SH2 binding interactions. The observed mode of binding to the Fyn-SH3 domain is expected to preclude the auto-inhibited conformation of Fyn, thereby promoting activation of the kinase after recruitment. These findings broaden our understanding of the functional repertoire of SH3 and SH2 domains.


  • Organizational Affiliation

    Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SH2 domain protein 1A104Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O60880 (Homo sapiens)
Explore O60880 
Go to UniProtKB:  O60880
PHAROS:  O60880
GTEx:  ENSG00000183918 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60880
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Signaling lymphocytic activation molecule11N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13291 (Homo sapiens)
Explore Q13291 
Go to UniProtKB:  Q13291
PHAROS:  Q13291
GTEx:  ENSG00000117090 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13291
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase FYN61Homo sapiensMutation(s): 0 
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P06241 (Homo sapiens)
Explore P06241 
Go to UniProtKB:  P06241
PHAROS:  P06241
GTEx:  ENSG00000010810 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06241
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FLC
Query on FLC

Download Ideal Coordinates CCD File 
D [auth A]CITRATE ANION
C6 H5 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.213 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.909α = 90
b = 52.909β = 90
c = 183.079γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-05-06
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations