1gxc
From Proteopedia
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| , resolution 2.70Å | |||||||
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FHA DOMAIN FROM HUMAN CHK2 KINASE IN COMPLEX WITH A SYNTHETIC PHOSPHOPEPTIDE
Contents |
Overview
The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.
Disease
Known diseases associated with this structure: Breast and colorectal cancer, susceptibility to OMIM:[604373], Breast cancer, susceptibility to OMIM:[604373], Li-Fraumeni syndrome OMIM:[604373], Osteosarcoma, somatic OMIM:[604373], Prostate cancer, familial OMIM:[604373]
About this Structure
1GXC is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2., Li J, Williams BL, Haire LF, Goldberg M, Wilker E, Durocher D, Yaffe MB, Jackson SP, Smerdon SJ, Mol Cell. 2002 May;9(5):1045-54. PMID:12049740
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