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

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 (PPlase) 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.This work was supported by grants from Ministerio de Educación y Cultura (PB98-1631 and 2FD97-0518), CSIC and Generalitat de Catalunya (CERBA and 1999SGR188) to M.C., grant PB98-0479 to A.G. and by grant BIO2000-1659 to F.X.G.-R. P.J.B.P. and S.M.-R. acknowledge postdoctoral fellowships from FCT (Portugal). Data collection at DESY was supported by EC grants ERBFMGECT980134 and HPRI-CT-1999-00017 to EMBL-HamburgPeer Reviewe

Coherent state quantization of a particle in de Sitter space

We present a coherent state quantization of the dynamics of a relativistic test particle on a one-sheet hyperboloid embedded in a three-dimensional Minkowski space. The group SO_0(1,2) is considered to be the symmetry group of the system. Our procedure relies on the choice of coherent states of the motion on a circle. The coherent state realization of the principal series representation of SO_0(1,2) seems to be a new result.Comment: Journal of Physics A: Mathematical and General, vol. 37, in pres

Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial

Objective To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts

Non-isothermal model for the direct isotropic/smectic-A liquid crystalline transition

An extension to a high-order model for the direct isotropic/smectic-A liquid crystalline phase transition was derived to take into account thermal effects including anisotropic thermal diffusion and latent heat of phase-ordering. Multi-scale multi-transport simulations of the non-isothermal model were compared to isothermal simulation, showing that the presented model extension corrects the standard Landau-de Gennes prediction from constant growth to diffusion-limited growth, under shallow quench/undercooling conditions. Non-isothermal simulations, where meta-stable nematic pre-ordering precedes smectic-A growth, were also conducted and novel non-monotonic phase-transformation kinetics observed.Comment: First revision: 20 pages, 7 figure