PMID:11751578

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Citation

Pereira, PJ, Vega, MC, González-Rey, E, Fernández-Carazo, R, Macedo-Ribeiro, S, Gomis-Rüth, FX, González, A and Coll, M (2002) Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix. EMBO Rep. 3:88-94

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.

Links

PubMed PMC1083928 Online version:10.1093/embo-reports/kvf009

Keywords

Amino Acid Sequence; Animals; Bacterial Proteins; Binding Sites; Humans; Immunophilins/chemistry; Macrophages; Membrane Proteins/chemistry; Models, Molecular; Molecular Sequence Data; Peptidylprolyl Isomerase/chemistry; Protein Structure, Secondary; Protozoan Proteins/chemistry; Protozoan Proteins/physiology; Sequence Homology; Sequence Homology, Amino Acid; Tacrolimus Binding Proteins/chemistry; Trypanosoma cruzi/chemistry; Trypanosoma cruzi/enzymology; Trypanosoma cruzi/physiology

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