PDBsum entry 2eyx

Signaling protein

PDB id: 2eyx

Contents

Protein chain

67 a.a. *

* Residue conservation analysis

PDB id:

2eyx

Name:

Signaling protein

Title:

C-terminal sh3 domain of ct10-regulated kinase

Structure:

V-crk sarcoma virus ct10 oncogene homolog isoform a. Chain: a. Fragment: c-terminal sh3 domain. Synonym: ct10-regulated kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

1 models

Authors:

Y.Kobashigawa,S.Tanaka,F.Inagaki

Key ref:

Y.Kobashigawa et al. (2007). Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK. Nat Struct Mol Biol, 14, 503-510. PubMed id: 17515907 DOI: 10.1038/nsmb1241

Date:

10-Nov-05 Release date: 10-Nov-06

Protein chain

P46108  (CRK_HUMAN) -  Adapter molecule crk from Homo sapiens

Seq: 304 a.a.

Struc: 67 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb1241

Nat Struct Mol Biol 14:503-510 (2007)

PubMed id: 17515907

Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.

Y.Kobashigawa, M.Sakai, M.Naito, M.Yokochi, H.Kumeta, Y.Makino, K.Ogura, S.Tanaka, F.Inagaki.

ABSTRACT

CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK that regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. CRKI shows substantial transforming activity, whereas the activity of CRKII is low, and phosphorylated CRKII has no biological activity whatsoever. The molecular mechanisms underlying the distinct biological activities of the CRK proteins remain elusive. We determined the solution structures of CRKI, CRKII and phosphorylated CRKII by NMR and identified the molecular mechanism that gives rise to their activities. Results from mutational analysis using rodent 3Y1 fibroblasts were consistent with those from the structural studies. Together, these data suggest that the linker region modulates the binding of CRKII to its targets, thus regulating cell growth and motility.

Selected figure(s)

Figure 1.
Figure 1. NMR structures of CRKI, CRKII and pCRKII[1–228]. (a) Domain structures. Tyr221 is the cABL phosphorylation site. (b–d) Superpositions of 20 lowest-energy structures of CRKI SH2 (b, left), CRKI SH3 (b, right), CRKII (c), pCRKII[1–228] SH2 (d, left) and pCRKII[1–228] nSH3 (d, right). Magenta, SH2 (residues 10–120); green, nSH3 (134–191); blue, cSH3 (238–293); yellow, ISC (220–237) (e) Ribbon representation of CRKII (left) and pCRKII[1–228] (right), colored as in b–d. In both structures, nSH3 is presented in the same orientation; ligand-binding sites in SH2 and SH3 are circled (dotted circle in CRKII represents putative binding site of cSH3). In pCRKII, the inter-SH2-nSH3 linker (121–133) is colored orange and the phosphorylation site (221–224) is cyan.

Figure 2.
Figure 2. Interdomain interactions in CRKII and pCRKII[1–228]. (a) Ribbon model of hydrophobic core of CRKII, between the ISC and the SH domains, colored as in Figure 1. Side chains of hydrophobic core are shown as sticks. (b) Interaction surfaces between SH2 and nSH3 in CRKII (left), and between the C3G peptide and nSH3 in CRKII (right). (c) Electrostatic surface potential (blue, positive; red, negative) of SH2 in pCRKII[1–228] and its recognition of 221-pYAQP-224 (shown as stick model). (d) Electrostatic surface potential of nSH3 in pCRKII[1–228] and its recognition of the inter-SH2-SH3 region (stick model).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2007, 14, 503-510) copyright 2007.

Figures were selected by an automated process.