Meleppattu, ShimiArthanari, HaribabuZinoviev, AlexandraBoeszoermenyi, AndrasWagner, GerhardShapira, MichalLeger-Abraham, Melissa2018-05-302018Meleppattu, Shimi, Haribabu Arthanari, Alexandra Zinoviev, Andras Boeszoermenyi, Gerhard Wagner, Michal Shapira, and Mélissa Léger-Abraham. 2018. “Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major.” Nucleic Acids Research 46 (7): 3791-3801. doi:10.1093/nar/gky194. http://dx.doi.org/10.1093/nar/gky194.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37068182Abstract Leishmania parasites are unicellular pathogens that are transmitted to humans through the bite of infected sandflies. Most of the regulation of their gene expression occurs post-transcriptionally, and the different patterns of gene expression required throughout the parasites’ life cycle are regulated at the level of translation. Here, we report the X-ray crystal structure of the Leishmania cap-binding isoform 1, LeishIF4E-1, bound to a protein fragment of previously unknown function, Leish4E-IP1, that binds tightly to LeishIF4E-1. The molecular structure, coupled to NMR spectroscopy experiments and in vitro cap-binding assays, reveal that Leish4E-IP1 allosterically destabilizes the binding of LeishIF4E-1 to the 5′ mRNA cap. We propose mechanisms through which Leish4E-IP1-mediated LeishIF4E-1 inhibition could regulate translation initiation in the human parasite.en-USJournal Article2018-05-3010.1093/nar/gky194