Solution structure of RING finger-like domain of retinoblastoma-binding protein-6 (RBBP6) suggests it functions as a U-box

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dc.contributor.authorKappo, M. A.
dc.contributor.authorAb, E.
dc.contributor.authorHassem, F.
dc.contributor.authorAtkinson, R. A.
dc.contributor.authorFaro, A.
dc.contributor.authorMuleya, V.
dc.contributor.authorMulaudzi, T.
dc.contributor.authorPoole, J. O.
dc.contributor.authorMcKenzie, J. M.
dc.contributor.authorChibi, M.
dc.contributor.authorMoolman-Smook, J. C.
dc.contributor.authorRees, D. J. G.
dc.contributor.authorPugh, D. J. R.
dc.date.accessioned2012-04-12T08:21:53Z
dc.date.available2012-04-12T08:21:53Z
dc.date.issued2012
dc.description.abstractRetinoblastoma-binding protein-6 (RBBP6) plays a facilitating role, through its RING finger-like domain, in the ubiquitination of p53 by Hdm2 that is suggestive of E4-like activity. Although the presence of eight conserved cysteine residues makes it highly probable that theRINGfinger-like domain coordinates two zinc ions, analysis of the primary sequence suggests an alternative classification as a member of the U-box family, the members of which do not bind zinc ions. We show here that despite binding two zinc ions, the domain adopts a homodimeric structure highly similar to those of a number of U-boxes. Zinc ions could be replaced by cadmium ions without significantly disrupting the structure or the stability of the domain, although the rate of substitution was an order of magnitude slower than any previous measurement, suggesting that the structure is particularly stable, a conclusion supported by the high thermal stability of the domain. A hallmark of U-box-containing proteins is their association with chaperones, with which they cooperate in eliminating irretrievably unfolded proteins by tagging them for degradation by the proteasome. Using a yeast two-hybrid screen, we show that RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. Taken together with the structural similarities to U-box-containing proteins, our data suggest that RBBP6 plays a role in chaperone-mediated ubiquitination and possibly in protein quality control. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
dc.identifier.citationJournal of Biological Chemistry
dc.identifier.citation287
dc.identifier.citation10
dc.identifier.citation7146
dc.identifier.citation7158
dc.identifier.issn219258
dc.identifier.other10.1074/jbc.M110.217059
dc.identifier.urihttp://hdl.handle.net/10019.1/20599
dc.titleSolution structure of RING finger-like domain of retinoblastoma-binding protein-6 (RBBP6) suggests it functions as a U-box
dc.typeArticle
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