1GXC

FHA domain from human Chk2 kinase in complex with a synthetic phosphopeptide

Summary for 1GXC

• Entry DOI: 10.2210/pdb1gxc/pdb
• Descriptor: SERINE/THREONINE-PROTEIN KINASE CHK2, SYNTHETIC PHOSPHOPEPTIDE (3 entities in total)
• Functional Keywords: phosphoprotein-binding domain, checkpoint kinase, transferase, serine/threonine-protein kinase
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Isoform 2: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 9: Nucleus. Isoform 12: Nucleus. Nucleus, PML body: O96017
• Total number of polymer chains: 8
• Total formula weight: 75587.18

Authors

Li, J.,Williams, B.L.,Haire, L.F.,Goldberg, M.,Wilker, E.,Durocher, D.,Yaffe, M.B.,Jackson, S.P.,Smerdon, S.J. (deposition date: 2002-04-02, release date: 2002-06-13, Last modification date: 2024-10-23)

Primary citation

Li, J.,Williams, B.L.,Haire, L.F.,Goldberg, M.,Wilker, E.,Durocher, D.,Yaffe, M.B.,Jackson, S.P.,Smerdon, S.J.
Structural and Functional Versatility of the Fha Domain in DNA-Damage Signaling by the Tumor Suppressor Kinase Chk2
Mol.Cell, 9:1045-, 2002

PubMed Abstract: 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.

PubMed: 12049740
DOI: 10.1016/S1097-2765(02)00527-0

Experimental method

X-RAY DIFFRACTION (2.7 Å)