title: Degradation of some polyubiquitinated proteins requires an intrinsic proteasomal binding element in the substrates.
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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Minglian
authors.initials: M
authors.lastname: Zhao
authors.forename: Nan-Yan
authors.initials: NY
authors.lastname: Zhang
authors.forename: Ashley
authors.initials: A
authors.lastname: Zurawel
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Liu
mesh_terms: D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D002850:Chromatography, Gel; D002942:Circular Dichroism; D013058:Mass Spectrometry; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D025821:Polyubiquitin; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex