5WB5

Leishmania IF4E-1 bound to Leishmania 4E-IP1

Summary for 5WB5

• Entry DOI: 10.2210/pdb5wb5/pdb
• Descriptor: Putative eukaryotic translation initiation factor eIF-4E, Uncharacterized protein, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: initiation factors, leishmania, parasites, cap, translation
• Biological source: Leishmania major; More
• Total number of polymer chains: 2
• Total formula weight: 30290.45

Authors

Leger-Abraham, M.,Meleppattu, S.,Arthanari, H.,Zinoviev, A.,Boeszoermenyi, A.,Wagner, G.,Shapira, M. (deposition date: 2017-06-27, release date: 2018-03-14, Last modification date: 2023-10-04)

Primary citation

Meleppattu, S.,Arthanari, H.,Zinoviev, A.,Boeszoermenyi, A.,Wagner, G.,Shapira, M.,Leger-Abraham, M.
Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major.
Nucleic Acids Res., 46:3791-3801, 2018

PubMed Abstract: 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.

PubMed: 29562352
DOI: 10.1093/nar/gky194

Experimental method

X-RAY DIFFRACTION (2.7 Å)