Structural and phylogenetic analysis of Trypanosoma cruzi´s major intrinsic proteins (MIP)

TESAN FIORELLA; ARMENTIA LUCIANO; ZEIDA ARIEL; ZERBETTO DE PALMA GG; PENAS F; FOX ANA ROMINA; LORENZO LOPEZ, JUAN RAMIRO; GOREN N; ALLEVA, KARINA

Virtual

Congreso; Annual Molecular Parasitology Meeting; 2020

Genetic Society of America

The rise in genome and transcriptome sequencing revealed a greatdiversity of aquaglyceroporins (Glp) and aquaporins (Aqp) (MIP, MajorIntrinsic Protein superfamily) throughout the three domains of life:Archaea, Bacteria and Eukarya. Some of these channels, first identifiedas water transporters, also transport solutes such as glycerol, hydrogenperoxide, etc. Also, some of these channels are involved in theinternalization of antiparasitic drugs in kinetoplastids: pentamidine forTrypanosoma brucei (T. brucei) and trivalent antimony for Leishmania.Trypanosoma cruzi (Tc) genomes encodes four AQPs but there are onlypartial functional results for one of them. Thus, the aim of this work is tocharacterize the structure of TcAQPs to gain knowledge on theirstructure-function particularities and to study their evolutionary context.AQP compatible sequences were searched for within Trytripdb and NCBIdatabases (annotated as AQP or resulted from tblastn search). Multiplesequence alignments (MAFFT, v7) were performed to build phylogenetictrees (Maximum Likelihood). Synteny studies were performed for thoseTrytripdb retrieved sequences. 3D models were built for the 4 TcAQP(Brener NEL stain) by ab initio methods (Rosetta, iTasser) and poreswere characterized based on molecular dynamics results (AMBER14SBand LIPID14 force field; Hole). Conserved AQP like tetrameric structureswere shown by all constructed 3D models.MIP asymmetry was found to be the distinctive feature betweenamerican and african trypanosomas (not only T. brucei and T. cruzi) withthe exception of T. grayi. For most of the other Trypanosomatida generawe found both Aqp and Glp MIPs. By syntenic analysis we concludedAqps coding regions were lost in african trypanosomes and Glps codingregions were lost in american trypanosomes. From the key MIP residuesanalysis, Trypanosomatida Aqps showed a classical AQP profile but hada nonclassical selectivity filter. Trypanosomatida Glps showed a classicalGlp and selectivity filter residue profiles. This work introduces a deeperunderstanding of the MIP superfamily and may help to elucidate itsfunctional role in the Trypanosomatida order, further functional analysisof the transport and localization of each TcAQP is still needed.