Figure 1: Conformation of proteasomal propeptides.
From: A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome
(a) Structural superposition of the β1-T1A propeptide and the matured WT β1 active-site Thr1. Only the residues (-5) to (-1) of the β1-T1A propeptide are displayed. The major determinant of the S1 specificity pocket, residue 45, is depicted. Note the tight conformation of Gly(-1) and Ala1 before propeptide removal (G(-1) turn; cyan double arrow) compared with the relaxed, processed WT active-site Thr1 (red double arrow). The black arrow indicates the attack of Thr1Oγ onto the carbonyl carbon atom of Gly(-1). (b) Structural superposition of the β1-T1A propeptide and the β2-T1A propeptide highlights subtle differences in their conformations, but illustrates that Ala1 and Gly(-1) match well. Thr(-2)OH is hydrogen-bonded to Gly(-1)O (∼2.8 Å; black dashed line). The major determinant of the S1 specificity pocket, residue 45, is depicted. (c) Structural superposition of the β1-T1A, the β2-T1A and the β5-T1A-K81R propeptide remnants depict their differences in conformation. While residue (-2) of the β1 and β2 prosegments fit the S1 pocket, His(-2) of the β5 propeptide occupies the S2 pocket. Nonetheless, in all mutants the carbonyl carbon atom of Gly(-1) is ideally placed for the nucleophilic attack by Thr1Oγ. The hydrogen bond between Thr(-2)OH and Gly(-1)O (∼2.8 Å) is indicated by a black dashed line.
