2W3O

Crystal structure of the human PNKP FHA domain in complex with an XRCC1-derived phosphopeptide

Summary for 2W3O

• Entry DOI: 10.2210/pdb2w3o/pdb
• Related: 1CDZ 1XNA 1XNT 2BRF 2D8M
• Descriptor: BIFUNCTIONAL POLYNUCLEOTIDE PHOSPHATASE/KINASE, DNA REPAIR PROTEIN XRCC1, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: hydrolase, transferase/peptide, fha, pnkp, xrcc1, kinase, nucleus, polynucleotide kinase 3' phosphatase, dna damage, dna repair, transferase, atp-binding, multifunctional enzyme, polymorphism, phosphoprotein, phospho- peptide, nucleotide-binding, base excision repair, transferase-peptide complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q96T60 P18887
• Total number of polymer chains: 4
• Total formula weight: 26507.24

Authors

Oliver, A.W.,Ali, A.A.E.,Pearl, L.H. (deposition date: 2008-11-13, release date: 2009-02-03, Last modification date: 2024-10-16)

Primary citation

Ali, A.A.E.,Jukes, R.M.,Pearl, L.H.,Oliver, A.W.
Specific Recognition of a Multiply Phosphorylated Motif in the DNA Repair Scaffold Xrcc1 by the Fha Domain of Human Pnk.
Nucleic Acids Res., 37:1701-, 2009

PubMed Abstract: Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the polymerase and ligase reactions respectively. PNK binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain. We show here, contrary to previous studies, that the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes.

PubMed: 19155274
DOI: 10.1093/NAR/GKN1086

Experimental method

X-RAY DIFFRACTION (1.85 Å)