The human mast cell tryptase tetramer: a fascinating riddle solved by structure

Tryptases, the predominant proteins of human mast cells, have been implicat ed as pathogenetic mediators of allergic and inflammatory conditions, most notably asthma. Until recently, the fascinating properties that distinguish tryptases among the serine proteinases, particularly their activity as a h eparin-stabilized tetramer, resistance to most proteinaceous inhibitors, an d preference for peptidergic over macromolecular substrates presented a rid dle. This review solves this riddle with the help of the crystal structure of the human beta(2)-tryprase tetramer, but also indicates controversies be tween the unique quaternary architecture and some experimental data. (C) 20 00 Elsevier Science B.V. All rights reserved.