4HTP

Crystal structure of the DBD domain of human DNA ligase IV bound to Artemis peptide

Summary for 4HTP

• Entry DOI: 10.2210/pdb4htp/pdb
• Descriptor: DNA ligase 4, Protein artemis (3 entities in total)
• Functional Keywords: helical domain, dna binding domain, dna, artemis, ligase-hydrolase complex, ligase/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P49917 Q96SD1
• Total number of polymer chains: 4
• Total formula weight: 57596.63

Authors

De Ioannes, P.E.,Aggarwal, A.K. (deposition date: 2012-11-01, release date: 2012-12-26, Last modification date: 2024-10-09)

Primary citation

De Ioannes, P.,Malu, S.,Cortes, P.,Aggarwal, A.K.
Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining.
Cell Rep, 2:1505-1512, 2012

PubMed Abstract: DNA ligase IV (LigIV) and Artemis are central components of the nonhomologous end-joining (NHEJ) machinery that is required for V(D)J recombination and the maintenance of genomic integrity in mammalian cells. We report here crystal structures of the LigIV DNA binding domain (DBD) in both its apo form and in complex with a peptide derived from the Artemis C-terminal region. We show that LigIV interacts with Artemis through an extended hydrophobic surface. In particular, we find that the helix α2 in LigIV-DBD is longer than in other mammalian ligases and presents residues that specifically interact with the Artemis peptide, which adopts a partially helical conformation on binding. Mutations of key residues on the LigIV-DBD hydrophobic surface abolish the interaction. Together, our results provide structural insights into the specificity of the LigIV-Artemis interaction and how the enzymatic activities of the two proteins may be coordinated during NHEJ.

PubMed: 23219551
DOI: 10.1016/j.celrep.2012.11.004

Experimental method

X-RAY DIFFRACTION (2.2502 Å)