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| | ==Crystal Structure of FHA domain of human APLF== | | ==Crystal Structure of FHA domain of human APLF== |
| - | <StructureSection load='5w7w' size='340' side='right' caption='[[5w7w]], [[Resolution|resolution]] 1.35Å' scene=''> | + | <StructureSection load='5w7w' size='340' side='right'caption='[[5w7w]], [[Resolution|resolution]] 1.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w7w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W7W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W7W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w7w]] 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=5W7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W7W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.348Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-(apurinic_or_apyrimidinic_site)_lyase DNA-(apurinic or apyrimidinic site) lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.99.18 4.2.99.18] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5w7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7w OCA], [http://pdbe.org/5w7w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w7w RCSB], [http://www.ebi.ac.uk/pdbsum/5w7w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7w 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=5w7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w7w OCA], [https://pdbe.org/5w7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w7w RCSB], [https://www.ebi.ac.uk/pdbsum/5w7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w7w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/APLF_HUMAN APLF_HUMAN]] Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage.<ref>PMID:17396150</ref> <ref>PMID:17353262</ref> | + | [https://www.uniprot.org/uniprot/APLF_HUMAN APLF_HUMAN] Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage.<ref>PMID:17396150</ref> <ref>PMID:17353262</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5w7w" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5w7w" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Apurinic/apyrimidinic endonuclease 3D structures|Apurinic/apyrimidinic endonuclease 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kim, K]] | + | [[Category: Homo sapiens]] |
| - | [[Category: London, R E]] | + | [[Category: Large Structures]] |
| - | [[Category: Pedersen, L C]] | + | [[Category: Kim K]] |
| - | [[Category: Dna repair]] | + | [[Category: London RE]] |
| - | [[Category: Nhej]] | + | [[Category: Pedersen LC]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Scaffold protein]]
| + | |
| Structural highlights
Function
APLF_HUMAN Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage.[1] [2]
Publication Abstract from PubMed
Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr. These high pK values are characteristic of the polyanionic peptides typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced by residues flanking the crystallographically-defined recognition motif, apparently as a consequence of non-specific electrostatic interactions, supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain-dependent interaction of XRCC1 with APLF joins repair scaffolds that support single-strand break repair and non-homologous end joining (NHEJ). It is suggested that for double-strand DNA breaks that have initially formed a complex with PARP1 and its binding partner XRCC1, this interaction acts as a backup attempt to intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ factors.
Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications.,Kim K, Pedersen LC, Kirby TW, DeRose EF, London RE Nucleic Acids Res. 2017 Dec 1;45(21):12374-12387. doi: 10.1093/nar/gkx941. PMID:29059378[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, Yasui A. A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 2007 Apr 18;26(8):2094-103. Epub 2007 Mar 29. PMID:17396150 doi:http://dx.doi.org/10.1038/sj.emboj.7601663
- ↑ Iles N, Rulten S, El-Khamisy SF, Caldecott KW. APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. Mol Cell Biol. 2007 May;27(10):3793-803. Epub 2007 Mar 12. PMID:17353262 doi:http://dx.doi.org/MCB.02269-06
- ↑ Kim K, Pedersen LC, Kirby TW, DeRose EF, London RE. Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications. Nucleic Acids Res. 2017 Dec 1;45(21):12374-12387. doi: 10.1093/nar/gkx941. PMID:29059378 doi:http://dx.doi.org/10.1093/nar/gkx941
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