Kamionka Mariusz, Feigon Juli
Department of Chemistry and Biochemistry, 405 Hilgard Avenue, P.O. Box 951569, University of California, Los Angeles, California 90095-1569, USA.
Protein Sci. 2004 Sep;13(9):2370-7. doi: 10.1110/ps.04824304.
Rad23 proteins are involved both in the ubiquitin-proteasome pathway and in nucleotide excision repair (NER), but the relationship between these two pathways is not yet understood. The two human homologs of Rad23, hHR23A and B, are functionally redundant in NER and interact with xeroderma pigmentosum complementation group C (XPC) protein. The XPC-hHR23 complex is responsible for the specific recognition of damaged DNA, which is an early step in NER. The interaction of the XPC binding domain (XPCB) of hHR23A/B with XPC protein has been shown to be important for its optimal function in NER. We have determined the solution structure of XPCB of hHR23A. The domain consists of five amphipathic helices and reveals hydrophobic patches on the otherwise highly hydrophilic domain surface. The patches are predicted to be involved in interaction with XPC. The XPCB domain has limited sequence homology with any proteins outside of the Rad23 family except for sacsin, a protein involved in spastic ataxia of Charlevoix-Saguenay, which contains a domain with 35% sequence identity.
Rad23蛋白参与泛素-蛋白酶体途径和核苷酸切除修复（NER），但这两条途径之间的关系尚不清楚。Rad23的两个人类同源物hHR23A和B在NER中功能冗余，并与着色性干皮病互补组C（XPC）蛋白相互作用。XPC-hHR23复合物负责受损DNA的特异性识别，这是NER的早期步骤。hHR23A/B的XPC结合结构域（XPCB）与XPC蛋白的相互作用已被证明对其在NER中的最佳功能很重要。我们已经确定了hHR23A的XPCB的溶液结构。该结构域由五个两亲性螺旋组成，在其他高度亲水的结构域表面上显示出疏水斑块。这些斑块预计参与与XPC的相互作用。除了与参与魁北克-萨格奈痉挛性共济失调的蛋白质sacsin外，XPCB结构域与Rad23家族以外的任何蛋白质的序列同源性都有限，sacsin含有一个具有35%序列同一性的结构域。
