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The Acidic Tail of the Cdc34 Ubiquitin-conjugating Enzyme Functions in Both Binding to and Catalysis with Ubiquitin Ligase SCFC^(dc4*)

Kleiger, Gary and Hao, Bing and Mohl, Dane A. and Deshaies, Raymond J. (2009) The Acidic Tail of the Cdc34 Ubiquitin-conjugating Enzyme Functions in Both Binding to and Catalysis with Ubiquitin Ligase SCFC^(dc4*). Journal of Biological Chemistry, 284 (52). pp. 36012-36023. ISSN 0021-9258. PMCID PMC2794717.

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Ubiquitin ligases, together with their cognate ubiquitin-conjugating enzymes, are responsible for the ubiquitylation of proteins, a process that regulates a myriad of eukaryotic cellular functions. The first cullin-RING ligase discovered, yeast SCF^(Cdc4), functions with the conjugating enzyme Cdc34 to regulate the cell cycle. Cdc34 orthologs are notable for their highly acidic C-terminal extension. Here we confirm that the Cdc34 acidic C-terminal tail has a role in Cdc34 binding to SCF^(Cdc4) and makes a major contribution to the submicromolar K_m of Cdc34 for SCF^(Cdc4). Moreover, we demonstrate that a key functional property of the tail is its acidity. Our analysis also uncovers an unexpected new function for the acidic tail in promoting catalysis. We demonstrate that SCF is functional when Cdc34 is fused to the C terminus of Cul1 and that this fusion retains partial function even when the acidic tail has been deleted. The Cdc34-SCF fusion proteins that lack the acidic tail must interact in a fundamentally different manner than unfused SCF and wild type Cdc34, demonstrating that distinct mechanisms of E2 recruitment to E3, as is seen in nature, can sustain substrate ubiquitylation. Finally, a search of the yeast proteome uncovered scores of proteins containing highly acidic stretches of amino acids, hinting that electrostatic interactions may be a common mechanism for facilitating protein assembly.

Item Type:Article
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URLURL TypeDescription CentralArticle
Kleiger, Gary0000-0003-3924-1680
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Free via Open Access: OA. Received for publication, August 21, 2009, and in revised form, October 22, 2009. Published, JBC Papers in Press, October 29, 2009. This work was supported, in whole or in part, by National Institutes of Health Ruth Kirschstein Postdoctoral Fellowship F32 GM074471-01. We thank Jost Vielmetter and members of the Caltech PEC for protein expression. We thank Shu-ou Shan for expert advice on the kinetic analysis of the data and members of the Deshaies lab for comments on the manuscript.
Funding AgencyGrant Number
NIH Ruth Kirschstein Postdoctoral FellowshipF32 GM074471-01
Issue or Number:52
PubMed Central ID:PMC2794717
Record Number:CaltechAUTHORS:20100121-133925591
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17269
Deposited By: Ruth Sustaita
Deposited On:25 Jan 2010 22:31
Last Modified:09 Mar 2020 13:18

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