Reference: Haririnia A, et al. (2008) Mutations in the hydrophobic core of ubiquitin differentially affect its recognition by receptor proteins. J Mol Biol 375(4):979-96

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Abstract


Ubiquitin (Ub) is one of the most highly conserved signaling proteins in eukaryotes. In carrying out its myriad functions, Ub conjugated to substrate proteins interacts with dozens of receptor proteins that link the Ub signal to various biological outcomes. Here we report mutations in conserved residues of Ub's hydrophobic core that have surprisingly potent and specific effects on molecular recognition. Mutant Ubs bind tightly to the Ub-associated domain of the receptor proteins Rad23 and hHR23A but fail to bind the Ub-interacting motif present in the receptors Rpn10 and S5a. Moreover, chains assembled on target substrates with mutant Ubs are unable to support substrate degradation by the proteasome in vitro or sustain viability of yeast cells. The mutations have relatively little effect on Ub's overall structure but reduce its rigidity and cause a slight displacement of the C-terminal beta-sheet, thereby compromising association with Ub-interacting motif but not with Ub-associated domains. These studies emphasize an unexpected role for Ub's core in molecular recognition and suggest that the diversity of protein-protein interactions in which Ub engages placed enormous constraints on its evolvability.

Reference Type
Comparative Study | Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Haririnia A, Verma R, Purohit N, Twarog MZ, Deshaies RJ, Bolon D, Fushman D
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