XPD Helicase (3CRV)
From Proteopedia
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CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. | CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. | ||
| - | == Structure | + | == Structure == |
The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. | The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. | ||
Revision as of 23:47, 26 April 2016
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