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| | <StructureSection load='6lae' size='340' side='right'caption='[[6lae]], [[Resolution|resolution]] 2.81Å' scene=''> | | <StructureSection load='6lae' size='340' side='right'caption='[[6lae]], [[Resolution|resolution]] 2.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lae]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LAE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lae]] is a 4 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=6LAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LAE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.81Å</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=6lae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lae OCA], [http://pdbe.org/6lae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lae RCSB], [http://www.ebi.ac.uk/pdbsum/6lae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lae ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6lae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lae OCA], [https://pdbe.org/6lae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lae RCSB], [https://www.ebi.ac.uk/pdbsum/6lae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lae ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN]] Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:[http://omim.org/entry/278700 278700]]; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders.<ref>PMID:1339397</ref> <ref>PMID:1372103</ref> <ref>PMID:9671271</ref> | + | [https://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN] Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:[https://omim.org/entry/278700 278700]; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders.<ref>PMID:1339397</ref> <ref>PMID:1372103</ref> <ref>PMID:9671271</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN]] Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.<ref>PMID:19197159</ref> | + | [https://www.uniprot.org/uniprot/XPA_HUMAN XPA_HUMAN] Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.<ref>PMID:19197159</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jiang, Y L]] | + | [[Category: Jiang YL]] |
| - | [[Category: Li, C]] | + | [[Category: Li C]] |
| - | [[Category: Lian, F M]] | + | [[Category: Lian FM]] |
| - | [[Category: Qian, C]] | + | [[Category: Qian C]] |
| - | [[Category: Yang, F]] | + | [[Category: Yang F]] |
| - | [[Category: Yang, W]] | + | [[Category: Yang W]] |
| - | [[Category: Yang, X]] | + | [[Category: Yang X]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Nucleotide excision repair]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| Structural highlights
Disease
XPA_HUMAN Defects in XPA are a cause of xeroderma pigmentosum complementation group A (XP-A) [MIM:278700; also known as xeroderma pigmentosum type 1 (XP1). XP-A is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Group A patients show the most severe skin symptoms and progressive neurological disorders.[1] [2] [3]
Function
XPA_HUMAN Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.[4]
Publication Abstract from PubMed
XPA (Xeroderma pigmentosum complementation group A) is a core scaffold protein that plays significant roles in DNA damage verification and recruiting downstream endonucleases in the nucleotide excision repair (NER) pathway. Here, we present the 2.81 A resolution crystal structure of the DNA-binding domain (DBD) of human XPA in complex with an undamaged splayed-arm DNA substrate with a single pair of non-complementary nucleotides. The structure reveals that two XPA molecules bind to one splayed-arm DNA with a 10-bp duplex recognition motif in a non-sequence-specific manner. XPA molecules bind to both ends of the DNA duplex region with a characteristic beta-hairpin. A conserved tryptophan residue Trp175 packs against the last base pair of DNA duplex and stabilizes the conformation of the characteristic beta-hairpin. Upon DNA binding, the C-terminal last helix of XPA would shift towards the minor groove of the DNA substrate for better interaction. Notably, human XPA is able to bind to the undamaged DNA duplex without any kinks, and XPA-DNA binding does not bend the DNA substrate obviously. This study provides structural basis for the binding mechanism of XPA to the undamaged splayed-arm DNA with a single pair of non-complementary nucleotides.
New structural insights into the recognition of undamaged splayed-arm DNA with a single pair of non-complementary nucleotides by human nucleotide excision repair protein XPA.,Lian FM, Yang X, Jiang YL, Yang F, Li C, Yang W, Qian C Int J Biol Macromol. 2020 Jan 18;148:466-474. doi:, 10.1016/j.ijbiomac.2020.01.169. PMID:31962067[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Satokata I, Tanaka K, Okada Y. Molecular basis of group A xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene. Hum Genet. 1992 Mar;88(6):603-7. PMID:1339397
- ↑ Satokata I, Tanaka K, Yuba S, Okada Y. Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum. Mutat Res. 1992 Mar;273(2):203-12. PMID:1372103
- ↑ States JC, McDuffie ER, Myrand SP, McDowell M, Cleaver JE. Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein. Hum Mutat. 1998;12(2):103-13. PMID:9671271 doi:<103::AID-HUMU5>3.0.CO;2-6 10.1002/(SICI)1098-1004(1998)12:2<103::AID-HUMU5>3.0.CO;2-6
- ↑ Pan YR, Lee EY. UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity. Cell Cycle. 2009 Feb 15;8(4):655-64. Epub 2009 Feb 14. PMID:19197159
- ↑ Lian FM, Yang X, Jiang YL, Yang F, Li C, Yang W, Qian C. New structural insights into the recognition of undamaged splayed-arm DNA with a single pair of non-complementary nucleotides by human nucleotide excision repair protein XPA. Int J Biol Macromol. 2020 Jan 18;148:466-474. doi:, 10.1016/j.ijbiomac.2020.01.169. PMID:31962067 doi:http://dx.doi.org/10.1016/j.ijbiomac.2020.01.169
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