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Reference: Kleiger G, et al. (2009) The Acidic Tail of the Cdc34 Ubiquitin-conjugating Enzyme Functions in Both Binding to and Catalysis with Ubiquitin Ligase SCFCdc4. J Biol Chem 284(52):36012-23

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Abstract


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 (CRL) 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 sub-micromolar Km 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 Cul1s C-terminus 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 un-fused 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.

Reference Type
Journal Article
Authors
Kleiger G, Hao B, Mohl DA, Deshaies RJ
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