2BRF

Crystal Structure of the FHA Domain of Human Polynucleotide Kinase 3' Phosphatase

Summary for 2BRF

• Entry DOI: 10.2210/pdb2brf/pdb
• Descriptor: BIFUNCTIONAL POLYNUCLEOTIDE PHOSPHATASE/KINASE, SULFATE ION (3 entities in total)
• Functional Keywords: hydrolase/transferase, fha, forkhead-associated, pnkp, pnk, polynucleotide kinase 3' phosphatase, dna repair, ber, ssbr, dsbr, xrcc1, xrcc4 hydrolase, transferase, bifunctional, hydrolase-transferase complex
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: Q96T60
• Total number of polymer chains: 1
• Total formula weight: 12001.48

Authors

Oliver, A.W.,Ali, A.A.E.,Pearl, L.H. (deposition date: 2005-05-04, release date: 2005-05-09, Last modification date: 2023-12-13)

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 (1.4 Å)