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PDBsum entry 1wyx

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protein ligands metals Protein-protein interface(s) links
Cell adhesion PDB id
1wyx
Jmol
Contents
Protein chains
68 a.a. *
Ligands
EDO
Metals
_MG
Waters ×165
* Residue conservation analysis
PDB id:
1wyx
Name: Cell adhesion
Title: The crystal structure of the p130cas sh3 domain at 1.1 a resolution
Structure: Crk-associated substrate. Chain: a, b. Fragment: sh3 domain. Synonym: crk-associated tyrosine kinase substrate p130cas, cas, p130cas, breast cancer anti-estrogen resistance 1 protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.14Å     R-factor:   0.177     R-free:   0.191
Authors: M.Wisniewska,B.Bossenmaier,G.Georges,F.Hesse,M.Dangl, K.P.Kuenkele,I.Ioannidis,R.Huber,R.A.Engh
Key ref:
M.Wisniewska et al. (2005). The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity. J Mol Biol, 347, 1005-1014. PubMed id: 15784259 DOI: 10.1016/j.jmb.2005.02.017
Date:
17-Feb-05     Release date:   26-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P56945  (BCAR1_HUMAN) -  Breast cancer anti-estrogen resistance protein 1
Seq:
Struc:
 
Seq:
Struc:
870 a.a.
68 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     signal transducer activity     1 term  

 

 
DOI no: 10.1016/j.jmb.2005.02.017 J Mol Biol 347:1005-1014 (2005)
PubMed id: 15784259  
 
 
The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity.
M.Wisniewska, B.Bossenmaier, G.Georges, F.Hesse, M.Dangl, K.P.Künkele, I.Ioannidis, R.Huber, R.A.Engh.
 
  ABSTRACT  
 
The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking protein containing an SH3 domain near its N terminus, followed by a short proline-rich segment, a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP, a serine-rich region and a carboxy-terminal domain, which possesses consensus binding sites for the SH2 and SH3 domains of Src (YDYV and RPLPSPP, respectively). The SH3 domain of CAS mediates its interaction with several proteins involved in signaling pathways such as focal adhesion kinase (FAK), tyrosine phosphatases PTP1B and PTP-PEST, and the guanine nucleotide exchange factor C3G. As a homolog of the corresponding Src docking domain, the CAS SH3 domain binds to proline-rich sequences (PxxP) of its interacting partners that can adopt a polyproline type II helix. We have determined a high-resolution X-ray structure of the recombinant human CAS SH3 domain. The domain, residues 1-69, crystallized in two related space groups, P2(1) and C222(1), that provided diffraction data to 1.1 A and 2.1 A, respectively. The crystal structure shows, in addition to the conserved SH3 domain architecture, the way in which the CAS characteristic amino acids form an atypically charged ligand-binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by the CAS SH3 domain. The structure enables modelling of the docking interactions to its ligands, for example from focal adhesion kinase, and supports structure-based drug design of inhibitors of the CAS-FAK interaction.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. The CA traces of the superposed SH3 domains of CAS (green, cyan and blue indicate the monomer, chain A and B, respectively), PI3K (orange) and a-spectrin (red).
Figure 7.
Figure 7. Model of the FAK peptide bound to the CAS SH3 domain. (a) Peptide residues are shown in green and numbered from 1 to 9. Residues that are involved in ligand binding are shown in ball and stick representation (the highly conserved amino acid residues are in cyan). (b) The CA traces of the superposed CAS SH3-FAK peptide complex (magenta) and C-Src SH3-App12 complex (cyan) (1QWE).31 (c) Interface of the CAS SH3-peptide complex interactions. SH3 domain is shown as a surface plot (residues in red, negatively charged; blue, positively charged; white, neutral), FAK peptide is shown in green.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 347, 1005-1014) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20084418 K.Prymula, K.SaƂapa, and I.Roterman (2010).
"Fuzzy oil drop" model applied to individual small proteins built of 70 amino acids.
  J Mol Model, 16, 1269-1282.  
19937461 N.Tikhmyanova, J.L.Little, and E.A.Golemis (2010).
CAS proteins in normal and pathological cell growth control.
  Cell Mol Life Sci, 67, 1025-1048.  
21102636 S.Cabodi, M.del Pilar Camacho-Leal, P.Di Stefano, and P.Defilippi (2010).
Integrin signalling adaptors: not only figurants in the cancer story.
  Nat Rev Cancer, 10, 858-870.  
18256281 M.K.Singh, D.Dadke, E.Nicolas, I.G.Serebriiskii, S.Apostolou, A.Canutescu, B.L.Egleston, and E.A.Golemis (2008).
A novel Cas family member, HEPL, regulates FAK and cell spreading.
  Mol Biol Cell, 19, 1627-1636.  
17367393 B.Bommarius, D.Maxwell, A.Swimm, S.Leung, A.Corbett, W.Bornmann, and D.Kalman (2007).
Enteropathogenic Escherichia coli Tir is an SH2/3 ligand that recruits and activates tyrosine kinases required for pedestal formation.
  Mol Microbiol, 63, 1748-1768.  
17129785 Y.Sawada, M.Tamada, B.J.Dubin-Thaler, O.Cherniavskaya, R.Sakai, S.Tanaka, and M.P.Sheetz (2006).
Force sensing by mechanical extension of the Src family kinase substrate p130Cas.
  Cell, 127, 1015-1026.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.