This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2r9a

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:46, 25 October 2017

Crystal structure of human XLF

Structural highlights

2r9a is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	NHEJ1, XLF (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NHEJ1_HUMAN] Defects in NHEJ1 are the cause of severe combined immunodeficiency due to NHEJ1 deficiency (NHEJ1-SCID) [MIM:611291]; also known as autosomal recessive T-cell-negative, B-cell-negative, NK cell-positive, severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation or NHEJ1 syndrome. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. NHEJ1-SCID is characterized by a profound T- and B-lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 mutations.^[1] ^[2] ^[3] ^[4] Note=A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22).^[5]

Function

[NHEJ1_HUMAN] DNA repair protein involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. May serve as a bridge between XRCC4 and the other NHEJ factors located at DNA ends, or may participate in reconfiguration of the end bound NHEJ factors to allow XRCC4 access to the DNA termini. It may act in concert with XRCC6/XRCC5 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are noncomplementary or partially complementary.^[6] ^[7] ^[8]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Crystal structure of human XLF: a twist in nonhomologous DNA end-joining.,Andres SN, Modesti M, Tsai CJ, Chu G, Junop MS Mol Cell. 2007 Dec 28;28(6):1093-101. PMID:18158905^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Buck D, Malivert L, de Chasseval R, Barraud A, Fondaneche MC, Sanal O, Plebani A, Stephan JL, Hufnagel M, le Deist F, Fischer A, Durandy A, de Villartay JP, Revy P. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell. 2006 Jan 27;124(2):287-99. PMID:16439204 doi:S0092-8674(06)00002-X
↑ Ahnesorg P, Smith P, Jackson SP. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell. 2006 Jan 27;124(2):301-13. PMID:16439205 doi:S0092-8674(06)00003-1
↑ Lu H, Pannicke U, Schwarz K, Lieber MR. Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity. J Biol Chem. 2007 Apr 13;282(15):11155-62. Epub 2007 Feb 21. PMID:17317666 doi:M609904200
↑ Dai Y, Kysela B, Hanakahi LA, Manolis K, Riballo E, Stumm M, Harville TO, West SC, Oettinger MA, Jeggo PA. Nonhomologous end joining and V(D)J recombination require an additional factor. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2462-7. Epub 2003 Feb 25. PMID:12604777 doi:10.1073/pnas.0437964100
↑ Dai Y, Kysela B, Hanakahi LA, Manolis K, Riballo E, Stumm M, Harville TO, West SC, Oettinger MA, Jeggo PA. Nonhomologous end joining and V(D)J recombination require an additional factor. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2462-7. Epub 2003 Feb 25. PMID:12604777 doi:10.1073/pnas.0437964100
↑ Buck D, Malivert L, de Chasseval R, Barraud A, Fondaneche MC, Sanal O, Plebani A, Stephan JL, Hufnagel M, le Deist F, Fischer A, Durandy A, de Villartay JP, Revy P. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell. 2006 Jan 27;124(2):287-99. PMID:16439204 doi:S0092-8674(06)00002-X
↑ Ahnesorg P, Smith P, Jackson SP. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell. 2006 Jan 27;124(2):301-13. PMID:16439205 doi:S0092-8674(06)00003-1
↑ Tsai CJ, Kim SA, Chu G. Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc Natl Acad Sci U S A. 2007 May 8;104(19):7851-6. Epub 2007 Apr 30. PMID:17470781 doi:0702620104
↑ Andres SN, Modesti M, Tsai CJ, Chu G, Junop MS. Crystal structure of human XLF: a twist in nonhomologous DNA end-joining. Mol Cell. 2007 Dec 28;28(6):1093-101. PMID:18158905 doi:http://dx.doi.org/10.1016/j.molcel.2007.10.024

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r9a"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human XLF==
 <StructureSection load='2r9a' size='340' side='right' caption='[[2r9a]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NHEJ1, XLF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9a OCA], [http://pdbe.org/2r9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r9a RCSB], [http://www.ebi.ac.uk/pdbsum/2r9a PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r9a OCA], [http://pdbe.org/2r9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r9a RCSB], [http://www.ebi.ac.uk/pdbsum/2r9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2r9a ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r9a ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 37: / Line 38: @@
 [[Category: Andres, S N]]
 [[Category: Junop, M S]]
+[[Category: Alternative splicing]]
 [[Category: Cernunno]]
 [[Category: Disease mutation]]

2r9a

From Proteopedia

Revision as of 07:46, 25 October 2017

Crystal structure of human XLF

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox