Kinetoplastid RNA editing ligases 1 and 2 exhibit different electrostatic properties
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ORIGINAL PAPER
Kinetoplastid RNA editing ligases 1 and 2 exhibit different electrostatic properties Alireza Shaneh & Reza Salavati
Received: 18 December 2008 / Accepted: 23 March 2009 / Published online: 27 May 2009 # Springer-Verlag 2009
Abstract Kinetoplastid RNA editing ligases 1 and 2 (KREL1 and KREL2) share a significant degree of sequence homology. However, biochemical experiments have reported that KREL1 and KREL2 differ in their functional roles during the RNA editing process. In this study, we hypothesize that dissimilar roles for KREL1 and KREL2 proteins arise from their different physicochemical characteristics. To test our hypothesis at sequence level, we plotted theoretical titration curves for KREL1, KREL2 and their binding partner proteins. The plots showed a lower isoelectric point for KREL1 compared to that for KREL2 as well as more relative alkalinity and acidity for binding partner proteins of KREL1 and KREL2 at net charge zero, respectively. At structure level, based on the available high resolution structure of KREL1 N-terminal domain and strong sequence similarity between KRELs and other ligases, we built the homology model of KREL2 Nterminal domain. Using Poisson-Boltzmann continuum approach, we calculated the electrostatic potential isosurfaces of KREL1 structure and KREL2 model. KREL1 and KREL2 coordinates differed in their electrostatic isopotential patterns. A wider negative patch on the surface of KREL1 suggests differential affinity for another protein compared to KREL2. In contrast, a larger positive patch on the KREL2 surface predicts its differential affinity and/or specificity for its RNA substrate. Subsequently, we employed in silico mutational scanning and identified the Electronic supplementary material The online version of this article (doi:10.1007/s00894-009-0506-1) contains supplementary material, which is available to authorized users. A. Shaneh : R. Salavati (*) Institute of Parasitology, McGill Centre for Bioinformatics, 21–111 Lakeshore Road, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada e-mail: [email protected]
surface-exposed residues contributing to the long-range electrostatic energy of KRELs. We predict that two structurally conserved loops of KRELs, not previously reported in the literature, also recognize their RNA substrates. Our results provide important information about the physicochemical properties of RNA editing ligases that could contribute to the ligation step of RNA editing. Keywords Editosome . Electrostatic potential energy . Homology modeling . Kinetoplastid RNA editing ligases . Poisson-Boltzmann equation . RNA editing
Introduction Trypanosomatidae, a family of kinetoplastids, consist of pathogenic agents of human African trypanosomiasis, Chagas disease, and leishmaniasis in Africa, Latin America, and much of tropical and subtropical countries. Trypanosoma brucei, T. cruzi and Leishmania major are the three major trypanosomatids that undergo remarkable changes in their morphology during their insect and mammalian bloodstream life stages that
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