1p1a is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
RD23B_HUMAN Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.[1][2][3][4][5][6][7][8][9][10][11] Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with CETN2 appears to stabilize XPC. May protect XPC from proteasomal degradation.[12][13][14][15][16][17][18][19][20][21][22] The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.[23][24][25][26][27][28][29][30][31][32][33]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
hHR23B is the human homologue of the yeast protein RAD23 and is known to participate in DNA repair by stabilizing xeroderma pigmentosum group C protein. However, hHR23B and RAD23 also have many important functions related to general proteolysis. hHR23B consists of N-terminal ubiquitin-like (UbL), ubiquitin association 1 (UBA1), xeroderma pigmentosum group C binding, and UBA2 domains. The UBA domains interact with ubiquitin (Ub) and inhibit the assembly of polyubiquitin. On the other hand, the UbL domain interacts with the poly-Ub binding site 2 (PUbS2) domain of the S5a protein, which can carry polyubiquitinated substrates into the proteasome. We calculated the NMR structure of the UbL domain of hHR23B and determined binding surfaces of UbL and Ub to UBA1, UBA2, of hHR23B and PUbS2 of S5a by using chemical shift perturbation. Interestingly, the surfaces of UbL and Ub that bind to UBA1, UBA2, and PUbS2 are similar, consisting of five beta-strands and their connecting loops. This is the first report that an intramolecular interaction between UbL and UBA domains is possible, and this interaction could be important for the control of proteolysis by hHR23B. The binding specificities of UbL and Ub for PUbS1, PUbS2, and general ubiquitin-interacting motifs, which share the LALA motif, were evaluated. The UBA domains bind to the surface of Ub including Lys-48, which is required for multiubiquitin assembly, possibly explaining the observed inhibition of multiubiquitination by hHR23B. The UBA domains bind to UbL through electrostatic interactions supported by hydrophobic interactions and to Ub mainly through hydrophobic interactions supported by electrostatic interactions.
Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a.,Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS J Biol Chem. 2003 Sep 19;278(38):36621-7. Epub 2003 Jun 28. PMID:12832454[34]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
↑Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
↑Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
↑Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
↑Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:https://dx.doi.org/10.1101/gad.260003
↑Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:https://dx.doi.org/10.1042/BJ20090528
↑Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
↑Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
↑Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
↑Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
↑Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
↑Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
↑Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
↑Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
↑Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:https://dx.doi.org/10.1101/gad.260003
↑Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:https://dx.doi.org/10.1042/BJ20090528
↑Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
↑Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
↑Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
↑Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
↑Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223-32. PMID:9734359
↑Batty D, Rapic'-Otrin V, Levine AS, Wood RD. Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol. 2000 Jul 7;300(2):275-90. PMID:10873465 doi:10.1006/jmbi.2000.3857
↑Sugasawa K, Shimizu Y, Iwai S, Hanaoka F. A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2002 Jan 22;1(1):95-107. PMID:12509299
↑Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C. DNA bending by the human damage recognition complex XPC-HR23B. DNA Repair (Amst). 2003 Mar 1;2(3):325-36. PMID:12547395
↑Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:https://dx.doi.org/10.1101/gad.260003
↑Li X, Demartino GN. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem J. 2009 Jul 15;421(3):397-404. doi: 10.1042/BJ20090528. PMID:19435460 doi:https://dx.doi.org/10.1042/BJ20090528
↑Sugasawa K, Akagi J, Nishi R, Iwai S, Hanaoka F. Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning. Mol Cell. 2009 Nov 25;36(4):642-53. doi: 10.1016/j.molcel.2009.09.035. PMID:19941824 doi:10.1016/j.molcel.2009.09.035
↑Neher TM, Rechkunova NI, Lavrik OI, Turchi JJ. Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry. 2010 Feb 2;49(4):669-78. doi: 10.1021/bi901575h. PMID:20028083 doi:10.1021/bi901575h
↑Shimizu Y, Uchimura Y, Dohmae N, Saitoh H, Hanaoka F, Sugasawa K. Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of Protein-Protein Interactions. J Nucleic Acids. 2010 Jul 25;2010. pii: 805698. doi: 10.4061/2010/805698. PMID:20798892 doi:10.4061/2010/805698
↑Kim B, Ryu KS, Kim HJ, Cho SJ, Choi BS. Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. FEBS J. 2005 May;272(10):2467-76. PMID:15885096 doi:10.1111/j.1742-4658.2005.04667.x
↑Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS. Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a. J Biol Chem. 2003 Sep 19;278(38):36621-7. Epub 2003 Jun 28. PMID:12832454 doi:10.1074/jbc.M304628200
