Research
Chaperone-mediated Proteasome Assembly
1. How do chaperones mediate "nucleotide-dependentÌýswitches"Ìýto complete proteasome holoenzymes properly?
Chaperone-mediated proteasome assembly is an incredibly sophisticated process, which initiates with 2 chaperones (Nas6, Rpn14; red, green) and their cognate ATPase subunits, Rpt3 and Rpt6 (orange). We identified nucleotide-dependent activities of chaperones, using Nas6 (Gankyrin, onco-protein in humans). Nas6 alternates its steric hindrance against lid or CP, depending nucleotide-state of the bound ATPase (orange), untilÌýa heterohexameric ATPase ring assembly (orange) is complete. Currently, we are investigating whether and how Nas6 cooperatively actsÌýwith itsÌýneighboring chaperone, Rpn14 (green), in order to properly "switch" to late-stage intermediates, and to the final step of completing proteasome holoenzyme.Ìý