Proteasomal cleavage of substrate

The 26S proteasome complex consists of the 20S catalytic core particle which harbours the proteolytically active sites and the regulatory 19S particle which is responsible for substrate interaction. The 26S proteasomal cleavage generates a vast number (perhaps hundreds) of different peptides, depending on the length and sequence of the substrate protein. Only a small fraction of these peptides (nearly 10%) form the exact length to be presented by class I MHC; most (approximately 70%) are too short to bind. The remaining proteasome products (10-20%) are N-terminally extended precursors that require additional cleavage by cytosolic aminopeptidases for presentation by MHC class I molecules.

26S蛋白酶体复合体由20S催化核心颗粒组成，其中包含蛋白酶解活性位点，以及负责底物相互作用的调节性19S颗粒。26S蛋白酶体裂解可产生大量（或许数百种）不同的肽段，其数量取决于底物蛋白质的长度和序列。在这些肽段中，仅有极小部分（几乎10%）的长度与I类MHC呈递的长度相匹配；其中大部分（约70%）长度过短，无法结合。剩余的蛋白酶体产物（10-20%）为N端延伸的前体，需要通过细胞质氨基肽酶的进一步裂解，才能被I类MHC分子呈递。