Eukaryotic Cell doi:10.1128/EC.00230-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
eIF4E isoforms of Leishmania - binding specificities and potential roles
Yael Yoffe,
Joanna Zuberek,
Asaf Lerer,
Magdalena Lewdorowicz,
Janusz Stepinski,
Michael Altmann,
Edward Darzynkiewicz,
and
Michal Shapira*
Department of Life Sciences, Ben Gurion University of the Negev, P.O.Box 653 Beer Sheva 84105, Israel; Department of Biophysics, Institute of Experimental Physics, Warsaw University, 93 Zwirki & Wigury St. 02-089, Warsaw, Poland; Institut für Biochemie und Molekulare Medizin, Universität Bern, Bühlstr. 28, CH-3012 Bern, Switzerland
* To whom correspondence should be addressed. Email:
shapiram{at}bgu.ac.il.
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Abstract |
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The 5' cap structure of trypanosomatid mRNAs, denoted cap-4, is a complex structure that contains unusual modifications on the first four nucleotides. We examined the four eIF4E homologues found in the Leishmania genome database. These proteins, denoted LeishIF4E1-4, are located in the cytoplasm. They show only a limited degree of sequence homology with known eIF4Es and among themselves. However, computerized structure prediction suggests that the cap-binding pocket is conserved in each of the homologues, as confirmed by binding assays to m7GTP, cap-4 and its intermediates. LeishIF4E-1 and -4, each binds m7GTP and cap-4 comparably well, and only these two proteins could interact with the mammalian eIF4E binding protein 4EBP1, though with different efficiencies. 4EBP1 is a translation repressor that competes with eIF4G for the same residues on eIF4E, thus, LeishIF4E-1 and -4 are reasonable candidates for serving as translation factors. LeishIF4E-1 is more abundant in amastigotes, and also contains a typical 3' UTR element that is found in amastigote-specific genes. LeishIF4E-2 bound mainly to cap-4 and comigrated with polysomal fractions on sucrose gradients. Since the consensus eIF4E is usually found in 48S complexes, LeishIF4E-2 could possibly be associated with stabilization of trypanosomatid polysomes. LeishIF4E-3 bound mainly m7GTP, excluding its involvement in translation of cap-4 protected mRNAs. It comigrates with 80S complexes which are resistant to micrococcal nuclease, but its function is yet unknown. None of the isoforms can functionally complement the yeast eIF4E, indicating that despite their structural conservation, they are considerably diverged.
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