We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed a-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-dimen- sional 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.
- Subjects
TRYPANOSOMA cruzi; MACROPHAGES; PROTEINS; CHAGAS' disease; ETIOLOGY of diseases; IMMUNOSUPPRESSIVE agents
- Publication
EMBO Reports, 2002, Vol 3, Issue 1, p88
- ISSN
1469-221X
- Publication type
Report
- DOI
10.1093/embo-reports/kvf009