Fig. 2

Structures of the mammalian proteasome. a A simplified model of the proteasome regulatory particle 19S. The lid mainly de-ubiquitylates the captured substrates, while the base functions as substrate unfolding and translocation. Rpn11 serves as a de-ubiquitylating enzyme (DUB) en clon cleaving the polyubiquitin chain of substrates. Rpt1-6, an ATPase ring, is involved in substrate protein unfolding and translocation into the channel of the 20S. Rpn13 and Rpn10 (a lid subunit) serve as ubiquitin receptors. Rpn1 can bind to the ubiquitin shuttle receptors and cytoplasmic deubiquitinases. b A simplified model of the proteasome regulatory particle 11S, which is also termed PA28. It is an activator of the proteasome. c Assembly model of mammalian proteasome. 20S binding 19S at one or two ends generates the 26S proteasome (or 30S), with an ATP-dependent degradation of ubiquitinated substrates. Upon stimulation of interferon-γ (INF-γ), all three active subunits (β1, β2 and β5) of the constitutive 20S proteasome are replaced by close-proximity similar subunits (β1i, β2i and β5i, respectively) that bind to 11S to generate the immunoproteasome. The immunoproteasome responds to antigen presentation with a non-ATP-dependent degradation of non-ubiquitinated proteins