6lae

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the DNA-binding domain of human XPA in complex with DNA

Structural highlights

6lae is a 4 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 2.81Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6lae"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6lae is ON HOLD
+==Crystal structure of the DNA-binding domain of human XPA in complex with DNA==
+<StructureSection load='6lae' size='340' side='right'caption='[[6lae]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81&#8491;</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>
+== Disease ==
+[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 ==
+[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;">
+== 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.
-Authors:
+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<ref>PMID:31962067</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6lae" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Jiang YL]]
+[[Category: Li C]]
+[[Category: Lian FM]]
+[[Category: Qian C]]
+[[Category: Yang F]]
+[[Category: Yang W]]
+[[Category: Yang X]]

6lae

From Proteopedia

Current revision

Crystal structure of the DNA-binding domain of human XPA in complex with DNA

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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