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PDBsum entry 1ju5
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protein Protein-protein interface(s) links
Protein binding/transferase PDB id
1ju5

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
109 a.a. *
13 a.a. *
60 a.a. *
* Residue conservation analysis
PDB id:
1ju5
Name: Protein binding/transferase
Title: Ternary complex of an crk sh2 domain, crk-derived phophopeptide, and abl sh3 domain by nmr spectroscopy
Structure: Crk. Chain: a. Fragment: crk sh2 domain. Synonym: proto-oncogenE C-crk, adapter molecule crk, p38. Engineered: yes. Crk. Chain: b. Fragment: crk phosphopeptide. Synonym: proto-oncogenE C-crk, adapter molecule crk, p38.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Mus musculus. House mouse. Organism_taxid: 10090.
NMR struc: 1 models
Authors: L.W.Donaldson,T.Pawson,L.E.Kay,J.D.Forman-Kay
Key ref:
L.W.Donaldson et al. (2002). Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide. Proc Natl Acad Sci U S A, 99, 14053-14058. PubMed id: 12384576 DOI: 10.1073/pnas.212518799
Date:
23-Aug-01     Release date:   06-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P46108  (CRK_HUMAN) -  Adapter molecule crk from Homo sapiens
Seq:
Struc: 		304 a.a.
109 a.a.
Protein chain
Pfam   ArchSchema ?
Q64010  (CRK_MOUSE) -  Adapter molecule crk from Mus musculus
Seq:
Struc: 		304 a.a.
13 a.a.*
Protein chain
Pfam   ArchSchema ?
P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1130 a.a.
60 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain C: E.C.2.7.10.2  - non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
L-tyrosyl-[protein]
 + ATP
 = O-phospho-L-tyrosyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.212518799 Proc Natl Acad Sci U S A 99:14053-14058 (2002)
PubMed id: 12384576  
 
 
Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
L.W.Donaldson, G.Gish, T.Pawson, L.E.Kay, J.D.Forman-Kay.
 
  ABSTRACT  
 
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221 site. Conformational changes induced by phosphotyrosine recognition promote the binding of the Src homology 3 (SH3) domain of the Abl tyrosine kinase to a proline-rich loop located between the betaD and betaE strands of the SH2 domain (DE loop). We have determined the NMR solution structure of the ternary complex of the Abl SH3 domain with the Crk SH2 domain bound to a Crk pY221 phosphopeptide. The SH2 domain bridges two ligands that bind at distinct sites. The interaction between the Abl SH3 domain and the Crk SH2 domain is localized to a canonical eight-residue site within the DE loop. From (15)N relaxation experiments, the DE loop of the SH2 domain in the complex displays a significant degree of conformational freedom. The structural and dynamic data therefore indicate that these SH2 and SH3 domains do not assume a unique orientation with respect to one another; rather, they appear to be only tethered via the DE loop. Thus, SH2 domain-SH3 domain interactions do not require additional tertiary contacts or restriction of domain orientation when a recognition motif is presented in a mobile loop. This complex between the Abl SH3 domain, Crk SH2 domain, and Crk phosphopeptide is an example of the extremely modular nature of regulatory proteins that provides a rich repertoire of mechanisms for control of biological function.
 
  Selected figure(s)  
 
Figure 1.
Fig 1. The complex described in this study includes the Abl SH3 domain (green), the Crk SH2 domain (yellow), and a 13-aa phosphopeptide corresponding to the Crk SH2 internal binding site (blue). 		Figure 4.
Fig 4. (Upper) Detail of the Crk SH2 domain bound to the Crk phosphopeptide (residues 221-224) in the ternary complex. Residues observed to make contacts are highlighted. (Lower) Sequence comparison of Crk-II with homologues v-Crk and CrkL. The sequence of murine Crk-II corresponds to the protein fragment described in this study. Only Crk-II contains a binding site for the Abl SH3 domain (shaded box).
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21532593 J.H.Cho, V.Muralidharan, M.Vila-Perello, D.P.Raleigh, T.W.Muir, and A.G.Palmer (2011).
Tuning protein autoinhibition by domain destabilization.
  Nat Struct Mol Biol, 18, 550-555.  
21131971 P.Sarkar, T.Saleh, S.R.Tzeng, R.B.Birge, and C.G.Kalodimos (2011).
Structural basis for regulation of the Crk signaling protein by a proline switch.
  Nat Chem Biol, 7, 51-57.
PDB codes: 2l3p 2l3q 2l3s
21227701 T.Kaneko, S.S.Sidhu, and S.S.Li (2011).
Evolving specificity from variability for protein interaction domains.
  Trends Biochem Sci, 36, 183-190.  
20423990 J.E.Sylvester, and S.J.Kron (2010).
A bead-based activity screen for small-molecule inhibitors of signal transduction in chronic myelogenous leukemia cells.
  Mol Cancer Ther, 9, 1469-1481.  
19665973 J.H.Bae, E.D.Lew, S.Yuzawa, F.Tomé, I.Lax, and J.Schlessinger (2009).
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.
  Cell, 138, 514-524.
PDB codes: 3gqi 3gql
19307307 J.H.Seo, A.Suenaga, M.Hatakeyama, M.Taiji, and A.Imamoto (2009).
Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop.
  Mol Cell Biol, 29, 3076-3087.  
19426560 R.B.Birge, C.Kalodimos, F.Inagaki, and S.Tanaka (2009).
Crk and CrkL adaptor proteins: networks for physiological and pathological signaling.
  Cell Commun Signal, 7, 13.  
19269802 T.Hunter (2009).
Tyrosine phosphorylation: thirty years and counting.
  Curr Opin Cell Biol, 21, 140-146.  
18430742 L.Wang, and U.H.Sauer (2008).
OnD-CRF: predicting order and disorder in proteins using [corrected] conditional random fields.
  Bioinformatics, 24, 1401-1402.  
19001122 X.Huang, D.Wu, H.Jin, D.Stupack, and J.Y.Wang (2008).
Induction of cell retraction by the combined actions of Abl-CrkII and Rho-ROCK1 signaling.
  J Cell Biol, 183, 711-723.  
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.  
18079720 M.Sainlos, and B.Imperiali (2007).
Tools for investigating peptide-protein interactions: peptide incorporation of environment-sensitive fluorophores via on-resin derivatization.
  Nat Protoc, 2, 3201-3209.  
17317137 T.Pawson (2007).
Dynamic control of signaling by modular adaptor proteins.
  Curr Opin Cell Biol, 19, 112-116.  
17515907 Y.Kobashigawa, M.Sakai, M.Naito, M.Yokochi, H.Kumeta, Y.Makino, K.Ogura, S.Tanaka, and F.Inagaki (2007).
Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.
  Nat Struct Mol Biol, 14, 503-510.
PDB codes: 2dvj 2eyv 2eyw 2eyx 2eyy 2eyz
16793553 B.A.Liu, K.Jablonowski, M.Raina, M.Arcé, T.Pawson, and P.D.Nash (2006).
The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling.
  Mol Cell, 22, 851-868.  
16216358 J.Vaynberg, and J.Qin (2006).
Weak protein-protein interactions as probed by NMR spectroscopy.
  Trends Biotechnol, 24, 22-27.  
16990796 L.V.Kalia, G.M.Pitcher, K.A.Pelkey, and M.W.Salter (2006).
PSD-95 is a negative regulator of the tyrosine kinase Src in the NMDA receptor complex.
  EMBO J, 25, 4971-4982.  
16446784 T.Hou, K.Chen, W.A.McLaughlin, B.Lu, and W.Wang (2006).
Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.
  PLoS Comput Biol, 2, e1.  
12787753 J.H.Wang, and M.J.Eck (2003).
Assembling atomic resolution views of the immunological synapse.
  Curr Opin Immunol, 15, 286-293.  
12665586 L.Li, D.L.Guris, M.Okura, and A.Imamoto (2003).
Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases.
  Mol Cell Biol, 23, 2883-2892.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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