PDBsum entry 5e50

Lyase

PDB id: 5e50

Contents

Protein chains

111 a.a.

Ligands

ALA-TYR-ASP-GLU-SEP-TPO-ASP-GLU-GLU ×2

Metals

_MG ×2

Waters ×402

PDB id:

5e50

Name:

Lyase

Title:

Aplf/xrcc4 complex

Structure:

Aprataxin and pnk-like factor. Chain: a, b. Synonym: apurinic-apyrimidinic endonuclease aplf,pnk and aptx-like fha domain-containing protein,xrcc1-interacting protein 1. Engineered: yes. Xrcc4. Chain: c, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: aplf, c2orf13, palf, xip1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.38Å R-factor: 0.138 R-free: 0.174

Authors:

A.L.Cherry,S.J.Smerdon

Key ref:

A.L.Cherry et al. (2015). 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. PubMed id: 26519825 DOI: 10.1016/j.dnarep.2015.10.002

Date:

07-Oct-15 Release date: 18-Nov-15

Protein chains

Q8IW19  (APLF_HUMAN) -  Aprataxin and PNK-like factor from Homo sapiens

Seq: 511 a.a.

Struc: 111 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.-.-

DOI no: 10.1016/j.dnarep.2015.10.002

Dna Repair (amst) 35:116-125 (2015)

PubMed id: 26519825

Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains.

A.L.Cherry, T.J.Nott, G.Kelly, S.L.Rulten, K.W.Caldecott, S.J.Smerdon.

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.