3odt
Crystal structure of WD40 beta propeller domain of Doa1
Structural highlights
FunctionDOA1_YEAST Participates in the regulation of the ubiquitin conjugation pathway involving CDC48 by hindering multiubiquitination of substrates at the CDC48 chaperone. May act by preventing the interaction between CDC48 and the E4 enzyme UFD2, leading to prevent multiubiquitination of substrates and subsequent degradation. Essential for maintaining cellular ubiquitin levels.[1] [2] Publication Abstract from PubMedWD40-repeat beta-propellers are found in a wide range of proteins involved in distinct biological activities. We define a large subset of WD40 beta-propellers as a class of ubiquitin-binding domains. Using the beta-propeller from Doa1/Ufd3 as a paradigm, we find the conserved top surface of the Doa1 beta-propeller binds the hydrophobic patch of ubiquitin centered on residues I44, L8, and V70. Mutations that disrupt ubiquitin binding abrogate Doa1 function, demonstrating the importance of this interaction. We further demonstrate that WD40 beta-propellers from a functionally diverse set of proteins bind ubiquitin in a similar fashion. This set includes members of the F box family of SCF ubiquitin E3 ligase adaptors. Using mutants defective in binding, we find that ubiquitin interaction by the F box protein Cdc4 promotes its autoubiquitination and turnover. Collectively, our results reveal a molecular mechanism that may account for how ubiquitin controls a broad spectrum of cellular activities. WD40 repeat propellers define a ubiquitin-binding domain that regulates turnover of F box proteins.,Pashkova N, Gakhar L, Winistorfer SC, Yu L, Ramaswamy S, Piper RC Mol Cell. 2010 Nov 12;40(3):433-43. PMID:21070969[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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