Unknown

Dataset Information

0

Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix.


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.

SUBMITTER: Pereira PJ 

PROVIDER: S-EPMC1083928 | biostudies-literature | 2002 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix.

Pereira Pedro José Barbosa PJ   Vega M Cristina MC   González-Rey Elena E   Fernández-Carazo Rafael R   Macedo-Ribeiro Sandra S   Gomis-Rüth F Xavier FX   González Antonio A   Coll Miquel M  

EMBO reports 20011219 1


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  ...[more]

Similar Datasets

| S-EPMC10077492 | biostudies-literature
| S-EPMC8981591 | biostudies-literature
| S-EPMC3722317 | biostudies-literature
| S-EPMC1913453 | biostudies-literature
| S-EPMC7094052 | biostudies-literature
| S-EPMC5568413 | biostudies-literature
| S-EPMC3057850 | biostudies-literature
| S-EPMC2644763 | biostudies-literature
| S-EPMC6119340 | biostudies-literature
| S-EPMC10941204 | biostudies-literature