PDBsum entry 3ii6

Ligase/DNA binding protein

PDB id: 3ii6

Contents

Protein chains

201 a.a. *

256 a.a. *

Metals

_CL ×2

Waters ×281

* Residue conservation analysis

PDB id:

3ii6

Name:

Ligase/DNA binding protein

Title:

Structure of human xrcc4 in complex with the tandem brct domains of DNA ligaseiv.

Structure:

DNA repair protein xrcc4. Chain: a, b, c, d. Fragment: residues 1-203. Synonym: x-ray repair cross-complementing protein 4. Engineered: yes. Mutation: yes. DNA ligase 4. Chain: x, y. Fragment: c-terminal tandem brct domains, residues 654-911.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: xrcc4. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: lig4.

Resolution:

2.40Å R-factor: 0.240 R-free: 0.280

Authors:

S.Meesala,M.Junop

Key ref:

P.Y.Wu et al. (2009). Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4. Mol Cell Biol, 29, 3163-3172. PubMed id: 19332554

Date:

31-Jul-09 Release date: 11-Aug-09

Protein chains

Q13426  (XRCC4_HUMAN) -  DNA repair protein XRCC4 from Homo sapiens

Seq: 336 a.a.

Struc: 201 a.a.*

Protein chains

P49917  (DNLI4_HUMAN) -  DNA ligase 4 from Homo sapiens

Seq: 911 a.a.

Struc: 256 a.a.

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

Enzyme reactions

• Enzyme class: Chains X, Y: E.C.6.5.1.1 - Dna ligase (ATP).
• Reaction: ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho- (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Mol Cell Biol 29:3163-3172 (2009)

PubMed id: 19332554

Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4.

P.Y.Wu, P.Frit, S.Meesala, S.Dauvillier, M.Modesti, S.N.Andres, Y.Huang, J.Sekiguchi, P.Calsou, B.Salles, M.S.Junop.

ABSTRACT

Nonhomologous end-joining represents the major pathway used by human cells to repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to reseal DNA strands. Here we report the high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV. The structure differs from the homologous Saccharomyces cerevisiae complex and reveals an extensive DNA ligase IV binding interface formed by a helix-loop-helix structure within the inter-BRCT linker region, as well as significant interactions involving the second BRCT domain, which induces a kink in the tail region of XRCC4. We further demonstrate that interaction with the second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in cells, as well as to achieve efficient dominant-negative effects resulting in radiosensitization after ectopic overexpression of DNA ligase IV fragments in human fibroblasts. Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex.