The protease inhibitor chagasin of Trypanosoma cruzi adopts an immunoglobulin-type fold and may have arisen by horizontal gene transfer

Chagasin, a protein from Trypanosonia cruzi, is the first member of a new f amily of cysteine protease inhibitors. Despite its lack of significant sequ ence identity with known proteins, convincing structural models, using vari able light chain templates, could be constructed on the basis of threading results. Experimental support for the final structure came from inhibition data for overlapping oligopeptides spanning the chagasin sequence. Chagasin therefore exemplifies a new protease inhibitor structural class and a new natural use for an immunoglobulin-like domain. Limited sequence resemblance suggests that chagasin may represent the result of a rare horizontal gene transfer from host to parasite. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.