6j44

From Proteopedia

(Difference between revisions)

Revision as of 06:11, 29 May 2019

Crystal structure of the redefined DNA-binding domain of human XPA

Structural highlights

6j44 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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), a key scaffold protein in nucleotide excision repair (NER) pathway, is important in DNA damage verification and repair proteins recruitment. Earlier studies had mapped the minimal DNA-binding domain (MBD) of XPA to a region corresponding to residues 98-219. However, recent studies indicated that the region involving residues 98-239 is the redefined DNA-binding domain (DBD), which binds to DNA substrates with a much higher binding affinity than MBD and possesses a nearly identical binding affinity to the full-length XPA protein. However, the structure of the redefined DBD domain of XPA (XPA-DBD) remains to be investigated. Here, we present the crystal structure of XPA-DBD at 2.06A resolution. Structure of the C-terminal region of XPA has been extended by 21 residues (Arg211-Arg231) as compared with previously reported MBD structures. The structure reveals that the C-terminal extension (Arg211-Arg231) is folded as an alpha-helix with multiple basic residues. The positively charged surface formed in the last C-terminal helix suggests its critical role in DNA binding. Further structural analysis demonstrates that the last C-terminal region (Asp217-Thr239) of XPA-DBD might undergo a conformational change to directly bind to the DNA substrates. This study provides a structural basis for understanding the possible mechanism of enhanced DNA-binding affinity of XPA-DBD.

Structural characterization of the redefined DNA-binding domain of human XPA.,Lian FM, Yang X, Yang W, Jiang YL, Qian C Biochem Biophys Res Commun. 2019 May 12. pii: S0006-291X(19)30918-0. doi:, 10.1016/j.bbrc.2019.05.050. PMID:31092331^[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, Yang W, Jiang YL, Qian C. Structural characterization of the redefined DNA-binding domain of human XPA. Biochem Biophys Res Commun. 2019 May 12. pii: S0006-291X(19)30918-0. doi:, 10.1016/j.bbrc.2019.05.050. PMID:31092331 doi:http://dx.doi.org/10.1016/j.bbrc.2019.05.050

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/6j44"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6j44 is ON HOLD  until Paper Publication
+==Crystal structure of the redefined DNA-binding domain of human XPA==
+<StructureSection load='6j44' size='340' side='right'caption='[[6j44]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6j44]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J44 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>
+<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=6j44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j44 OCA], [http://pdbe.org/6j44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j44 RCSB], [http://www.ebi.ac.uk/pdbsum/6j44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j44 ProSAT]</span></td></tr>
+</table>
+== 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>
+== 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+XPA (xeroderma pigmentosum complementation group A), a key scaffold protein in nucleotide excision repair (NER) pathway, is important in DNA damage verification and repair proteins recruitment. Earlier studies had mapped the minimal DNA-binding domain (MBD) of XPA to a region corresponding to residues 98-219. However, recent studies indicated that the region involving residues 98-239 is the redefined DNA-binding domain (DBD), which binds to DNA substrates with a much higher binding affinity than MBD and possesses a nearly identical binding affinity to the full-length XPA protein. However, the structure of the redefined DBD domain of XPA (XPA-DBD) remains to be investigated. Here, we present the crystal structure of XPA-DBD at 2.06A resolution. Structure of the C-terminal region of XPA has been extended by 21 residues (Arg211-Arg231) as compared with previously reported MBD structures. The structure reveals that the C-terminal extension (Arg211-Arg231) is folded as an alpha-helix with multiple basic residues. The positively charged surface formed in the last C-terminal helix suggests its critical role in DNA binding. Further structural analysis demonstrates that the last C-terminal region (Asp217-Thr239) of XPA-DBD might undergo a conformational change to directly bind to the DNA substrates. This study provides a structural basis for understanding the possible mechanism of enhanced DNA-binding affinity of XPA-DBD.
-Authors:
+Structural characterization of the redefined DNA-binding domain of human XPA.,Lian FM, Yang X, Yang W, Jiang YL, Qian C Biochem Biophys Res Commun. 2019 May 12. pii: S0006-291X(19)30918-0. doi:, 10.1016/j.bbrc.2019.05.050. PMID:31092331<ref>PMID:31092331</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 6j44" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Jiang, Y L]]
+[[Category: Lian, F M]]
+[[Category: Qian, C]]
+[[Category: Yang, W]]
+[[Category: Yang, X]]
+[[Category: Dna binding protein]]
+[[Category: Dna repair]]
+[[Category: Nucleotide excision repair]]
+[[Category: Scaffold protein]]
+[[Category: Zinc finger]]

6j44

From Proteopedia

Revision as of 06:11, 29 May 2019

Crystal structure of the redefined DNA-binding domain of human XPA

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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