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2qm4
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The recently characterised 299-residue human XLF/Cernunnos protein plays a | + | 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 A 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ., Li Y, Chirgadze DY, Bolanos-Garcia VM, Sibanda BL, Davies OR, Ahnesorg P, Jackson SP, Blundell TL, EMBO J. 2007 Nov 29 | + | Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ., Li Y, Chirgadze DY, Bolanos-Garcia VM, Sibanda BL, Davies OR, Ahnesorg P, Jackson SP, Blundell TL, EMBO J. 2008 Jan 9;27(1):290-300. Epub 2007 Nov 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18046455 18046455] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Blundell, T | + | [[Category: Blundell, T L.]] |
| - | [[Category: Bolanos-Garcia, V | + | [[Category: Bolanos-Garcia, V M.]] |
| - | [[Category: Chirgadze, D | + | [[Category: Chirgadze, D Y.]] |
| - | [[Category: Davies, O | + | [[Category: Davies, O R.]] |
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
| - | [[Category: Sibanda, B | + | [[Category: Sibanda, B L.]] |
[[Category: beta-sandwich]] | [[Category: beta-sandwich]] | ||
[[Category: coiled-coil]] | [[Category: coiled-coil]] | ||
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[[Category: xrcc4 like factor]] | [[Category: xrcc4 like factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:40:24 2008'' |
Revision as of 16:40, 21 February 2008
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Crystal structure of human XLF/Cernunnos, a non-homologous end-joining factor
Overview
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 A 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.
About this Structure
2QM4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ., Li Y, Chirgadze DY, Bolanos-Garcia VM, Sibanda BL, Davies OR, Ahnesorg P, Jackson SP, Blundell TL, EMBO J. 2008 Jan 9;27(1):290-300. Epub 2007 Nov 29. PMID:18046455
Page seeded by OCA on Thu Feb 21 18:40:24 2008
