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Analysis of DNA damage recognition and repair factor (XPA) in Homo sapiens
Jeffrey Chimenti & Rory Vanderberg
Published: December 9, 2019
Protein Structure
Figure 1: 3D Structure of the DNA and RPA Binding domain of the Human Repair Factor XPA
(PDB ID: 1XPA)
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Source: [iCn3D: Web-Based 3D Structure Viewer] (4)
Figure 1: The structure shown above is the protein structure for the DNA and RPA binding domain of the human repair factor XPA (PDB accession number: 1XPA). This structure was founded with nuclear magnetic resonance (NMR) spectroscopy. The central domain is made up of a zinc-containing subdomain and a C-terminal subdomain. The subdomain containing the zinc has a small globular structure which defines it from the zinc-fingers found within the transcription factors. (6)
This XPA protein structure consists of one chain with a sequence length of 122 amino acids for the protein coding variant 'a'. The protein structure also consists of a zinc ion because the XPA gene encodes for a zinc finger protein that plays a critical role in nucleotide excision repair. PDBsum(6) shows that the 1XPA protein structure contains 2 sheets, 2 beta hairpins, 5 strands, 4 helices, 4 helix-helix interacs, 16 beta turns, and 4 gamma turns. This protein structure also contains 122 residues. (5)
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The secondary structure consists of each of the 4 helices, with no quaternary structure present. The active site of this structure is a zinc binding site with residues: CYS 105, CYS 108, CYS 126, and CYS 129 seen below in Figure 2.
Figure 2: Secondary Structures and Binding Sites in XPA Protein
Figure 3: Functional Domain XPA_C
Source: NCBI Conserved Protein Domain Family (8)
Figure 4: Functional Domain XPA_N
Source: NCBI Conserved Protein Domain Family (9)
Figures 3 and 4: AceView shows that the XPA protein has two functional domains, located on the 'C' and 'N' terminals called XPA_C and XPA_N respectively, present on both isoform variants 'a' and 'b'. XPA_C is the super family for the functional domains, containing 135-186 residues. Variant 'a' and 'b' both show that the XPA_N domain is located from 139 to 172 amino acids, and the XPA_C domain is located from 173 to 225 amino acids.
Xeroderma pigmentosum (XP) is the human autosomal recessive disease that correlates with a high incidence of sunlight-induced skin cancer (10). When an individual has this condition, it makes them more sensitive to ultra violet light because there is a defect in the incision step of DNA excision repair. The domains XPA_C and XPA_N interact only with each other to aid in the function of the protein by interacting with DNA and many nucleotide excision repair proteins.
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