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J. Biol. Chem., Vol. 278, Issue 38, 36621-36627, September 19, 2003

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 278/38/36621    most recent M304628200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ryu, K.-S. Articles by Choi, B.-S. Search for Related Content PubMed PubMed Citation Articles by Ryu, K.-S. Articles by Choi, B.-S. Social Bookmarking                      What's this?

Binding Surface Mapping of Intra- and Interdomain Interactions among hHR23B, Ubiquitin, and Polyubiquitin Binding Site 2 of S5a^*,

Kyoung-Seok Ryu , Kyung-Jin Lee, Sung-Hun Bae, Byoung-Kook Kim, Kyoung-Ah Kim and Byong-Seok Choi 

From the Yusong-Gu, Gusong-Dong 373-1, Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon 305-701, South Korea

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 -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.

Received for publication, May 2, 2003 , and in revised form, June 6, 2003.

The atomic coordinates and structure factors (code 1P1A) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Creative Research Initiative from Ministry of Science and Technology, the Republic of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplement 1, showing the secondary structure of PUbS2 bound on the UbL domain.

Supported by the BK21 project.

To whom correspondence should be addressed. Tel.: 82-42-869-2828; Fax: 82-42-869-2810; E-mail: byongseok.choi{at}webmail.kaist.ac.kr.

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