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- Title
Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix.
- Authors
Pereira, Pedro José Barbosa; Vega, M Cristina; González-Rey, Elena; Fernández-Carazo, Rafael; Macedo-Ribeiro, Sandra; Gomis-Rüth, F Xavier; González, Antonio; Coll, Miquel
- Abstract
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 A 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 beta-sheet of the core is extended by an extra beta-strand, preceded by a long, exposed N-terminal alpha-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 alpha-helix, can substitute for TcMIP. An additional exposed alpha-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.
- Publication
EMBO reports, 2002, Vol 3, Issue 1, p88
- ISSN
1469-221X
- Publication type
Journal Article
- DOI
10.1093/embo-reports/kvf009