Regulation of the 20S by the 19S

The 19S regulatory particle is responsible for stimulating the 20S to degrade proteins. A primary function of the 19S regulatory ATPases is to open the gate in the 20S that blocks the entry of substrates into the degradation chamber.[22] The mechanism by which the proteasomal ATPase open this gate has been recently elucidated.[14] 20S gate opening, and thus substrate degradation, requires the C-termini of the proteasomal ATPases, which contains a specific motif (i.e. HbYX motif). The ATPases C-termini bind into pockets in the top of the 20S, and tether the ATPase complex to the 20S proteolytic complex thus joining the substrate unfolding equipment with the 20S degradation machinery. Binding of these C-termini into these 20S pockets by themselves stimulates opening of the gate in the 20S much like a "key-in-a-lock" opens a door.[14] The precise mechanism by which this "key-in-a-lock" mechanism functions has been structurally elucidated.[23]
[edit]11S regulatory particle
20S proteasomes can also associate with a second type of regulatory particle, the 11S regulatory particle, a heptameric structure that does not contain any ATPases and can promote the degradation of short peptides, but not of complete proteins. It is presumed that this is because the complex cannot unfold larger substrates. This structure is also known as PA28 or REG. The mechanisms by which it binds to the core particle through the C-terminal tails of its subunits and induces α-ring conformational changes to open the 20S gate suggest a similar mechanism for the 19S particle.[24] The expression of the 11S particle is induced by interferon gamma and is responsible, in conjunction with the immunoproteasome β subunits, for the generation of peptides that bind to the major histocompatibility complex.[13]



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