Human Tumor Antigens and Cancer Immunotherapy

Figure 3

Proteasome activities. (a) Peptide-bond hydrolysis. In the course of peptide-bond hydrolysis, the hydroxyl group of the N-terminal threonine produces a nucleophile attack on the carbonyl of the peptide bond. This leads to the formation of an acyl-enzyme intermediate in which a peptide fragment remains attached to the proteasome through an ester link. Finally hydrolysis of the acyl-enzyme intermediate by a water molecule present in the proteasome chamber will restore the hydroxyl group of the catalytic threonine and release the peptide. (b) Peptide splicing by the proteasome. Splicing of the antigenic peptide RTK_QLYPEW derived from the differentiation antigen gp100. After formation of the acyl-enzyme intermediate involving the fragment RTK, the free N-terminal amino-group of peptide QLYPEW present in the proteasome chamber performs a nucleophilic attack on the acyl-enzyme intermediate. This leads to the creation of a new peptide bond, which assembles both fragments of the spliced peptide. Balls represent the catalytic β subunits of the proteasome. The hydroxyl group of the N-terminal threonine is indicated.

(a)

(b)