|
Figure 1.
Figure 1. Crystal structures of serpins shown as ribbon
representations. (a) The structure of antithrombin (PDB 1E05)
shows the A-sheet of the serpin (red) with entry of the reactive
loop (yellow) to P14. The crucial point of bifurcation of the
sheet at the site of entry of P8 is circled in blue. As shown in
b, A-sheet opening beyond P12 allows the insertion of the P8-P3
segment of the loop of another molecule (yellow) leading to
polymer formation. Model based on the structure of
a1-antichymotrypsin.28 (c) Antitrypsin can become polymerogenic
through cleavage of the reactive loop as observed
crystallographically.15^ and 16 The polymers are formed by
sequential insertion of the C-terminal portion of the reactive
loop of one molecule into the opened A-sheet of another. (d)
Antithrombin is rendered polymerogenic by annealing of P14-P8/9
peptides (dark blue) to the top of the sheet, but additional
annealing to P7-P4 of the peptide WMDF (light blue) blocks
polymerisation.
|
