|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of paFAN1 - 5' flap DNA complex with Manganase== | | ==Crystal structure of paFAN1 - 5' flap DNA complex with Manganase== |
| - | <StructureSection load='4r89' size='340' side='right' caption='[[4r89]], [[Resolution|resolution]] 4.00Å' scene=''> | + | <StructureSection load='4r89' size='340' side='right'caption='[[4r89]], [[Resolution|resolution]] 4.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r89]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R89 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R89 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r89]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R89 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 4.002Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r8a|4r8a]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4r89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r89 OCA], [http://pdbe.org/4r89 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r89 RCSB], [http://www.ebi.ac.uk/pdbsum/4r89 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r89 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=4r89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r89 OCA], [https://pdbe.org/4r89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r89 RCSB], [https://www.ebi.ac.uk/pdbsum/4r89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r89 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/FAN1_PSEAE FAN1_PSEAE] Nuclease required for the repair of DNA interstrand cross-links (ICL). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions. Also has endonuclease activity toward 5'-flaps (PubMed:25319828).[UniProtKB:Q9Y2M0]<ref>PMID:24981866</ref> <ref>PMID:25319828</ref> |
| - | Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI-FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5' flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domain playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.
| + | |
| - | | + | |
| - | Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1.,Gwon GH, Kim Y, Liu Y, Watson AT, Jo A, Etheridge TJ, Yuan F, Zhang Y, Kim Y, Carr AM, Cho Y Genes Dev. 2014 Oct 15;28(20):2276-90. doi: 10.1101/gad.248492.114. PMID:25319828<ref>PMID:25319828</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4r89" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cho, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Gwon, G H]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Kim, Y R]] | + | [[Category: Cho Y]] |
| - | [[Category: 5'flap dna endo nuclease]] | + | [[Category: Gwon GH]] |
| - | [[Category: Dna binding]] | + | [[Category: Kim YR]] |
| - | [[Category: Fanconi anemia proteins family]]
| + | |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Metal binding nuclease]]
| + | |
| Structural highlights
Function
FAN1_PSEAE Nuclease required for the repair of DNA interstrand cross-links (ICL). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions. Also has endonuclease activity toward 5'-flaps (PubMed:25319828).[UniProtKB:Q9Y2M0][1] [2]
References
- ↑ Pennell S, Declais AC, Li J, Haire LF, Berg W, Saldanha JW, Taylor IA, Rouse J, Lilley DM, Smerdon SJ. FAN1 activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain. Cell Rep. 2014 Jul 10;8(1):84-93. doi: 10.1016/j.celrep.2014.06.001. Epub 2014, Jun 26. PMID:24981866 doi:http://dx.doi.org/10.1016/j.celrep.2014.06.001
- ↑ Gwon GH, Kim Y, Liu Y, Watson AT, Jo A, Etheridge TJ, Yuan F, Zhang Y, Kim Y, Carr AM, Cho Y. Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1. Genes Dev. 2014 Oct 15;28(20):2276-90. doi: 10.1101/gad.248492.114. PMID:25319828 doi:http://dx.doi.org/10.1101/gad.248492.114
|
