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The most lethal form of leishmaniasis in mammals _ kala-azar or visceral leishmaniasis, is caused by the intracellular protozoan parasite Leishmania donovani. The several phases of infection and life cycle of the parasite are regulated by Rab proteins, a small GTPase subfamily. This study uses biophysical methods to describe the pH-moderated solution characteristics of a recombinant Rab1 isoform from L. donovani (rLdRab1). The isoform unfolds on lowering the solution pH in a non-two-state route, highlighting the potential for more than one folding intermediates. At pH 2.0, a partially folded intermediate (PFI) state accumulates and exhibits properties median to the molten and pre-molten globule states. At high protein concentrations the high amyloidogenic potential of this PFI induces slow transformation into distinct protofibrils. It was also noted that the native state of the isoform was aggregation-prone. Nevertheless, amorphous aggregation rather than fibrils was formed. This is the first work, to our knowledge, to describe the amyloid-like behaviour of Rab isoforms in L donovani in vitro. This research provides an unusual alternative to comprehend the full biophysical properties of the Rab1 isoforms in the lower eukaryote L. donovani. |
