3Q4F: Crystal Structure Of Xrcc4XLF-Cernunnos Complex

Citation:
Abstract
Cernunnos/XLF is a core protein of the nonhomologous DNA end-joining (NHEJ) pathway that processes the majority of DNA double-strand breaks in mammals. Cernunnos stimulates the final ligation step catalyzed by the complex between DNA ligase IV and Xrcc4 (X4). Here we present the crystal structure of the X4(1-157)-Cernunnos(1-224) complex at 5.5-A resolution and identify the relative positions of the two factors and their binding sites. The X-ray structure reveals a filament arrangement for X4(1-157) and Cernunnos(1-224) homodimers mediated by repeated interactions through their N-terminal head domains. A filament arrangement of the X4-Cernunnos complex was confirmed by transmission electron microscopy analyses both with truncated and full-length proteins. We further modeled the interface and used structure-based site-directed mutagenesis and calorimetry to characterize the roles of various residues at the X4-Cernunnos interface. We identified four X4 residues (Glu(55), Asp(58), Met(61), and Phe(106)) essential for the interaction with Cernunnos. These findings provide new insights into the molecular bases for stimulatory and bridging roles of Cernunnos in the final DNA ligation step.
PDB ID: 3Q4FDownload
MMDB ID: 92335
PDB Deposition Date: 2010/12/23
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 5.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3Q4F: tetrameric; determined by author
Molecular Components in 3Q4F
Label Count Molecule
Proteins (4 molecules)
2
Non-homologous End-joining Factor 1(Gene symbol: NHEJ1)
Molecule annotation
2
DNA Repair Protein Xrcc4(Gene symbol: XRCC4)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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