Dynamical insight into eIF4E recognition specificity for mono-and trimethylated structures of mRNA 5′ cap

Autor: Ruszczyńska-Bartnik, Katarzyna, Maciejczyk, Maciej, Stolarski, Ryszard
Přispěvatelé: Nuclear Magnetic Resonance Laboratory, Institute of Biochemistry and Biophysics, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Department of Physics and Biophysics, University of Warmia and Mazury, Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw (UW)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Journal of Molecular Modeling
Journal of Molecular Modeling, Springer Verlag (Germany), 2010, 17 (4), pp.727-737. ⟨10.1007/s00894-010-0773-x⟩
ISSN: 1610-2940
0948-5023
Popis: International audience; Specific recognition and binding of the ribonucleic acid 5′ termini (mRNA 5′ cap) by the eukaryotic translation initiation factor 4E (eIF4E) is a key, rate limiting step in translation initiation. Contrary to mammalian and yeast eIF4Es that discriminate in favor of 7-methylguanosine cap, three out of five eIF4E isoforms from the nematode as well as eIF4Es from the parasites and , exhibit dual binding specificity for both 7-methylguanosine-and N,N,7-trimethylguanosine cap. To address the problem of the differences in the mechanism of the cap recognition by those highly homologic proteins, we carried out molecular dynamics simulations in water of three factors, IFE-3 and IFE-5 isoforms from and murine eIF4E, in the form as well as in the complexes with 7-methyl-GDP and N,N,7-trimethyl-GDP. The results clearly pointed to a dynamical mechanism of discrimination between each type of the cap, . differences in mobility of the loops located at the entrance into the protein binding pockets during the cap association and dissociation. Additionally, our data showed that the hydrogen bond involving the N-amino group of 7-methylguanosine and the carboxylate of glutamic acid was not stable. The dynamic mechanism proposed here differs from a typical, static one in that the differences in the protein-ligand binding specificity cannot be ascribed to formation and/or disruption of well defined stabilizing contacts.
Databáze: OpenAIRE
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