Degradation of Some Polyubiquitinated Proteins Requires an Intrinsic Proteasomal Binding Element in the Substrates |
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Authors: | Minglian Zhao Nan-Yan Zhang Ashley Zurawel Kirk C. Hansen Chang-Wei Liu |
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Affiliation: | From the ‡Department of Biochemistry and Molecular Genetics and ;the §Proteomic Core Facility, University of Colorado Denver School of Medicine, Aurora, Colorado 80045 |
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Abstract: | Lysine 48-linked polyubiquitin chains usually target proteins for 26 S proteasomal degradation; however, this modification is not a warrant for destruction. Here, we found that efficient degradation of a physiological substrate UbcH10 requires not only an exogenous polyubiquitin chain modification but also its unstructured N-terminal region. Interestingly, the unstructured N-terminal region of UbcH10 directly binds the 19 S regulatory complex of the 26 S proteasome, and it mediates the initiation of substrate translocation. To promote ubiquitin- dependent degradation of the folded domains of UbcH10, its N-terminal region can be displaced by exogenous proteasomal binding elements. Moreover, the unstructured N-terminal region can initiate substrate translocation even when UbcH10 is artificially cyclized without a free terminus. Polyubiquitinated circular UbcH10 is completely degraded by the 26 S proteasome. Accordingly, we propose that degradation of some polyubiquitinated proteins requires two binding interactions: a polyubiquitin chain and an intrinsic proteasomal binding element in the substrates (likely an unstructured region); moreover, the intrinsic proteasomal binding element initiates substrate translocation regardless of its location in the substrates. |
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Keywords: | Protease/ATP-dependent Proteases/Proteasomes Proteases/Ubiqiuitin Proteases/Ubiquitination Protein/Degradation Protein/Processing |
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