5E50

APLF/XRCC4 complex

Summary for 5E50

• Entry DOI: 10.2210/pdb5e50/pdb
• Descriptor: Aprataxin and PNK-like factor, XRCC4, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: fha domain, aplf, xrcc4, complex, lyase
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: Q8IW19
• Total number of polymer chains: 4
• Total formula weight: 26658.52

Authors

Cherry, A.L.,Smerdon, S.J. (deposition date: 2015-10-07, release date: 2015-11-18, Last modification date: 2024-10-23)

Primary citation

Cherry, A.L.,Nott, T.J.,Kelly, G.,Rulten, S.L.,Caldecott, K.W.,Smerdon, S.J.
Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains.
DNA Repair (Amst.), 35:116-125, 2015

PubMed Abstract: Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them.

PubMed: 26519825
DOI: 10.1016/j.dnarep.2015.10.002

Experimental method

X-RAY DIFFRACTION (1.376 Å)