3zqs: Difference between revisions

Latest revision as of 11:10, 20 December 2023

Human FANCL central domain

Structural highlights

3zqs is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	NA, P6G, PRO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FANCL_HUMAN Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.

Function

FANCL_HUMAN Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The Fanconi Anemia (FA) pathway is essential for the repair of DNA interstrand cross-links. At the heart of this pathway is the monoubiquitination of the FANCI/FANCD2 (ID) complex by the multiprotein 'core complex' containing the E3 ubiquitin ligase FANCL. Vertebrate organisms have the 8-protein core complex, while invertebrates apparently do not. We report here the structure of the central domain of human FANCL in comparison with the recently solved Drosophila melanogaster FANCL. Our data represent the first structural detail into the catalytic core of the human system, and reveal that the central fold of FANCL is conserved between species. However, there are macromolecular differences between the FANCL proteins that may account for the apparent distinctions in core complex requirements between the vertebrate and invertebrate FA pathways. In addition we characterize the binding of human FANCL with its partners, Ube2t, FANCD2 and FANCI. Mutational analysis reveals, which residues are required for substrate binding, and we also show the domain required for E2 binding.

Structural analysis of human FANCL, the E3 ligase in the fanconi anemia pathway.,Hodson C, Cole AR, Lewis LP, Miles JA, Purkiss-Trew A, Walden H J Biol Chem. 2011 Jul 20. PMID:21775430^[6]

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

References

↑ Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W. A novel ubiquitin ligase is deficient in Fanconi anemia. Nat Genet. 2003 Oct;35(2):165-70. Epub 2003 Sep 14. PMID:12973351 doi:https://dx.doi.org/10.1038/ng1241
↑ Machida YJ, Machida Y, Chen Y, Gurtan AM, Kupfer GM, D'Andrea AD, Dutta A. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006 Aug;23(4):589-96. PMID:16916645 doi:https://dx.doi.org/10.1016/j.molcel.2006.06.024
↑ Alpi A, Langevin F, Mosedale G, Machida YJ, Dutta A, Patel KJ. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007 Dec;27(24):8421-30. Epub 2007 Oct 15. PMID:17938197 doi:https://dx.doi.org/10.1128/MCB.00504-07
↑ Alpi AF, Pace PE, Babu MM, Patel KJ. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008 Dec 26;32(6):767-77. doi: 10.1016/j.molcel.2008.12.003. PMID:19111657 doi:https://dx.doi.org/10.1016/j.molcel.2008.12.003
↑ Longerich S, San Filippo J, Liu D, Sung P. FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. J Biol Chem. 2009 Aug 28;284(35):23182-6. doi: 10.1074/jbc.C109.038075. Epub 2009, Jul 8. PMID:19589784 doi:https://dx.doi.org/10.1074/jbc.C109.038075
↑ Hodson C, Cole AR, Lewis LP, Miles JA, Purkiss-Trew A, Walden H. Structural analysis of human FANCL, the E3 ligase in the fanconi anemia pathway. J Biol Chem. 2011 Jul 20. PMID:21775430 doi:10.1074/jbc.M111.244632

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OCA

[1] Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W. A novel ubiquitin ligase is deficient in Fanconi anemia. Nat Genet. 2003 Oct;35(2):165-70. Epub 2003 Sep 14. PMID:12973351 doi:https://dx.doi.org/10.1038/ng1241

[2] Machida YJ, Machida Y, Chen Y, Gurtan AM, Kupfer GM, D'Andrea AD, Dutta A. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006 Aug;23(4):589-96. PMID:16916645 doi:https://dx.doi.org/10.1016/j.molcel.2006.06.024

[3] Alpi A, Langevin F, Mosedale G, Machida YJ, Dutta A, Patel KJ. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007 Dec;27(24):8421-30. Epub 2007 Oct 15. PMID:17938197 doi:https://dx.doi.org/10.1128/MCB.00504-07

[4] Alpi AF, Pace PE, Babu MM, Patel KJ. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008 Dec 26;32(6):767-77. doi: 10.1016/j.molcel.2008.12.003. PMID:19111657 doi:https://dx.doi.org/10.1016/j.molcel.2008.12.003

[5] Longerich S, San Filippo J, Liu D, Sung P. FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. J Biol Chem. 2009 Aug 28;284(35):23182-6. doi: 10.1074/jbc.C109.038075. Epub 2009, Jul 8. PMID:19589784 doi:https://dx.doi.org/10.1074/jbc.C109.038075

[6] Hodson C, Cole AR, Lewis LP, Miles JA, Purkiss-Trew A, Walden H. Structural analysis of human FANCL, the E3 ligase in the fanconi anemia pathway. J Biol Chem. 2011 Jul 20. PMID:21775430 doi:10.1074/jbc.M111.244632

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[6]

@@ Line 1: / Line 1: @@
-==HUMAN FANCL CENTRAL DOMAIN==
+==Human FANCL central domain==
-<StructureSection load='3zqs' size='340' side='right' caption='[[3zqs]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3zqs' size='340' side='right'caption='[[3zqs]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zqs]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZQS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zqs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZQS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PRO:PROLINE'>PRO</scene></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=3zqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zqs OCA], [http://pdbe.org/3zqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zqs RCSB], [http://www.ebi.ac.uk/pdbsum/3zqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zqs ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zqs OCA], [https://pdbe.org/3zqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zqs RCSB], [https://www.ebi.ac.uk/pdbsum/3zqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zqs ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/FANCL_HUMAN FANCL_HUMAN]] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/FANCL_HUMAN FANCL_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/FANCL_HUMAN FANCL_HUMAN]] Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.<ref>PMID:12973351</ref> <ref>PMID:16916645</ref> <ref>PMID:17938197</ref> <ref>PMID:19111657</ref> <ref>PMID:19589784</ref>
+[https://www.uniprot.org/uniprot/FANCL_HUMAN FANCL_HUMAN] Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.<ref>PMID:12973351</ref> <ref>PMID:16916645</ref> <ref>PMID:17938197</ref> <ref>PMID:19111657</ref> <ref>PMID:19589784</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
+*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ubiquitin--protein ligase]]
+[[Category: Large Structures]]
-[[Category: Cole, A R]]
+[[Category: Cole AR]]
-[[Category: Hodson, C]]
+[[Category: Hodson C]]
-[[Category: Purkiss-Trew, A]]
+[[Category: Purkiss-Trew A]]
-[[Category: Walden, H]]
+[[Category: Walden H]]
-[[Category: Ligase]]

3zqs: Difference between revisions

Latest revision as of 11:10, 20 December 2023

Human FANCL central domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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