NDLI: Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ

Content Provider	PubMed Central
Author	Li, Yi Chirgadze, Dimitri Y. Bolanos-garcia, Victor M. Sibanda, Bancinyane L. Davies, Owen R. Peter, Ahnesorg Jackson, Stephen P. Blundell, Tom L.
Copyright Year	2008
Abstract	The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4–DNA Ligase IV complex. Here, we report the crystal structure of the XLF (1–233) homodimer at 2.3 Å resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7601942
Ending Page	300
Page Count	11
Starting Page	290
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	1
Volume Number	27
Language	English
Publisher	Nature Publishing Group
Publisher Date	2008-01-09
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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