The protease inhibitor chagasin of Trypanosoma cruzi adopts an immunoglobulin-type fold and may have arisen by horizontal gene transfer.
Chagasin, a protein from Trypanosoma cruzi, is the first member of a new family of tight binding cysteine protease inhibitors [Monteiro, A.C.S., Abrahamson, M., Lima, A.P.C., Vannier-Santos, M.A. and Scharfstein, J. (2001) J. Cell Sci., in press] [corrected]. Despite its lack of significant sequence identity with known proteins, convincing structural models, using variable 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.
Rigden
D J
DJ
National Centre of Genetic Resources and Biotechnology, Cenargen/Embrapa, S.A.I.N. Parque Rural, Final W5 Norte, 70770-900, Brasilia, Brazil. daniel@cenargen.embrapa.br
Monteiro
A C
AC
Grossi de Sá
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000235:genetics; D022761:Gene Transfer, Horizontal; D007136:Immunoglobulins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014349:Trypanosoma cruzi / Q000737:chemistry*
D015853:Cysteine Proteinase Inhibitors; D007136:Immunoglobulins; D015800:Protozoan Proteins; C435145:chagasin, Trypanosoma