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Structural characterization reveals a novel bilobed architecture for the ectodomains of insect stage expressed Trypanosoma brucei PSSA‐2 and Trypanosoma congolense ISA
Author(s) -
Ramaswamy Raghavendran,
Goomeshi Nobary Sarah,
Eyford Brett A.,
Pearson Terry W.,
Boulanger Martin J.
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3053
Subject(s) - trypanosoma brucei , biology , trypanosoma , vector (molecular biology) , african trypanosomiasis , virology , microbiology and biotechnology , trypanosomiasis , genetics , gene , recombinant dna
African trypanosomiasis, caused by parasites of the genus Trypanosoma, is a complex of devastating vector‐borne diseases of humans and livestock in sub‐Saharan Africa. Central to the pathogenesis of African trypanosomes is their transmission by the arthropod vector, Glossina spp . (tsetse fly). Intriguingly, the efficiency of parasite transmission through the vector is reduced following depletion of Trypanosoma brucei Procyclic‐Specific Surface Antigen‐2 ( Tb PSSA‐2). To investigate the underlying molecular mechanism of Tb PSSA‐2, we determined the crystal structures of its ectodomain and that of its homolog T. congolense Insect Stage Antigen ( Tc ISA) to resolutions of 1.65 Å and 2.45 Å, respectively using single wavelength anomalous dispersion. Both proteins adopt a novel bilobed architecture with the individual lobes displaying rotational flexibility around the central tether that suggest a potential mechanism for coordinating a binding partner. In support of this hypothesis, electron density consistent with a bound peptide was observed in the inter‐lob cleft of a Tc ISA monomer. These first reported structures of insect stage transmembrane proteins expressed by African trypanosomes provide potentially valuable insight into the interface between parasite and tsetse vector.