TY - JOUR
T1 - Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major
AU - Meleppattu, Shimi
AU - Arthanari, Haribabu
AU - Zinoviev, Alexandra
AU - Boeszoermenyi, Andras
AU - Wagner, Gerhard
AU - Shapira, Michal
AU - Léger-Abraham, Mélissa
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2018/4/20
Y1 - 2018/4/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061161533&partnerID=8YFLogxK
U2 - 10.1093/nar/gky194
DO - 10.1093/nar/gky194
M3 - Article
C2 - 29562352
AN - SCOPUS:85061161533
SN - 0305-1048
VL - 46
SP - 3791
EP - 3801
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 7
ER -