2R9A

Crystal structure of human XLF

Summary for 2R9A

• Entry DOI: 10.2210/pdb2r9a/pdb
• Descriptor: Non-homologous end-joining factor 1 (2 entities in total)
• Functional Keywords: xlf, cernunnos, non-homologous end joining, dna double strand break repair, alternative splicing, disease mutation, dna damage, dna repair, nucleus, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q9H9Q4
• Total number of polymer chains: 2
• Total formula weight: 53416.80

Authors

Andres, S.N.,Junop, M.S. (deposition date: 2007-09-12, release date: 2008-01-01, Last modification date: 2024-11-20)

Primary citation

Andres, S.N.,Modesit, M.,Tsai, C.J.,Chu, G.,Junop, M.S.
Crystal Structure of Human XLF: A Twist in Nonhomologous DNA End-Joining
Mol.Cell, 28:1093-1101,

PubMed Abstract: DNA double-strand breaks represent one of the most severe forms of DNA damage in mammalian cells. One pathway for repairing these breaks occurs via nonhomologous end-joining (NHEJ) and depends on XRCC4, LigaseIV, and Cernunnos, also called XLF. Although XLF stimulates XRCC4/LigaseIV to ligate mismatched and noncohesive DNA ends, the mechanistic basis for this function remains unclear. Here we report the structure of a partially functional 224 residue N-terminal fragment of human XLF. Despite only weak sequence similarity, XLF(1-170) shares structural homology with XRCC4(1-159). However, unlike the highly extended 130 A helical domain observed in XRCC4, XLF adopts a more compact, folded helical C-terminal region involving two turns and a twist, wrapping back to the structurally conserved N terminus. Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends.

PubMed: 18158905
DOI: 10.1016/j.molcel.2007.10.024

Experimental method

X-RAY DIFFRACTION (2.5 Å)