Ubiquitin (Ub) specifically interacts with the Ub-associating domain () in a proteasomal shuttle factor, while the latter is involved in either proteasomal targeting or self-assembly coacervation. PINK1 at S65 and makes Ub alternate between C-terminally relaxed () and retracted conformations (). Using NMR spectroscopy, we show that but not preferentially interacts with the from two proteasomal shuttle factors Ubqln2 and Rad23A. Yet discriminatorily, Ubqln2- binds to more tightly than Rad23A does and selectively enriches upon complex formation. Further, we determine the solution structure of the complex between Ubqln2- and and uncover the thermodynamic basis for the stronger interaction. NMR kinetics analysis at different timescales further suggests an indued-fit binding mechanism for interaction. Notably, at a relatively low saturation level, the dissociation rate of the complex is comparable with the exchange rate between and . Thus, a kinetic constraint would dictate the interaction between Ub and , thus fine-tuning the functional state of the proteasomal shuttle factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301994 | PMC |
http://dx.doi.org/10.3390/biom11071008 | DOI Listing |
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