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Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed α‐helix
Author(s) -
Pereira Pedro José Barbosa,
Vega M Cristina,
GonzálezRey Elena,
FernándezCarazo Rafael,
MacedoRibeiro Sandra,
GomisRüth F Xavier,
González Antonio,
Coll Miquel
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf009
Subject(s) - infectivity , potentiator , trypanosoma cruzi , legionella pneumophila , biology , protein structure , peptidylprolyl isomerase , molecular mimicry , biochemistry , isomerase , virology , immunology , genetics , enzyme , bacteria , antibody , parasite hosting , virus , world wide web , computer science
The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three‐dimensional crystal structure of TcMIP at 1.7 Å resolution. The monomeric protein displays a peptidyl‐prolyl cis–trans isomerase (PPIase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted β‐sheet of the core is extended by an extra β‐strand, preceded by a long, exposed N‐terminal α‐helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N‐terminal α‐helix, can substitute for TcMIP. An additional exposed α‐helix, this one unique to TcMIP, is located in the C‐terminus of the protein. The high‐resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.