TY - JOUR
T1 - Two Structurally Atypical HEAT Domains in the C-Terminal Portion of Human eIF4G Support Binding to eIF4A and Mnk1
AU - Bellsolell, Lluís
AU - Cho-Park, Park F.
AU - Poulin, Francis
AU - Sonenberg, Nahum
AU - Burley, Stephen K.
N1 - Funding Information: We thank Dr. J.B. Bonanno for assistance with X-ray data measurement and phasing, Dr. G. He for preparation of eIF4G expression clones, and Ms. T.B. Niven for editorial assistance. We are also grateful to Drs. G. Bricogne, J. Cabral, R. Deo, C. Edo, A.-C. Gingras, D. Jeruzalmi, J. Kuriyan, D. Lubell, J. Marcotrigiano, M. Miron, S.K. Nair, G.A. Petsko, and B. Raught for useful discussions, and Drs. S. Wasserman and K. D'Amico for access to the COM-CAT beamline. N.S. is a CIHR Distinguished Investigator and a Howard Hughes Medical Institute International Scholar. This work was supported by National Institutes of Health grant GM61262 to S.K.B., and a grant from the CIHR to N.S. L.B. was supported by a Ministerio de Educacion y Ciencia (Spain) and a Human Frontiers Science Program fellowship. F.P. was supported by a Doctoral Research Award from the CIHR.
PY - 2006/5
Y1 - 2006/5
N2 - The X-ray structure of the C-terminal region of human eukaryotic translation initiation factor 4G (eIF4G) has been determined at 2.2 Å resolution, revealing two atypical HEAT-repeat domains. eIF4G recruits various translation factors and the 40S ribosomal subunit to the mRNA 5′ end. In higher eukaryotes, the C terminus of eIF4G (4G/C) supports translational regulation by recruiting eIF4A, an RNA helicase, and Mnk1, the kinase responsible for phosphorylating eIF4E. Structure-guided surface mutagenesis and protein-protein interaction assays were used to identify binding sites for eIF4A and Mnk1 within the HEAT-repeats of 4G/C. p97/DAP5, a translational modulator homologous to eIF4G, lacks an eIF4A binding site in the corresponding region. The second atypical HEAT domain of the 4G/C binds Mnk1 using two conserved aromatic/acidic-box (AA-box) motifs. Within the first AA-box, the aromatic residues contribute to the hydrophobic core of the domain, while the acidic residues form a negatively charged surface feature suitable for electrostatic interactions with basic residues in Mnk1.
AB - The X-ray structure of the C-terminal region of human eukaryotic translation initiation factor 4G (eIF4G) has been determined at 2.2 Å resolution, revealing two atypical HEAT-repeat domains. eIF4G recruits various translation factors and the 40S ribosomal subunit to the mRNA 5′ end. In higher eukaryotes, the C terminus of eIF4G (4G/C) supports translational regulation by recruiting eIF4A, an RNA helicase, and Mnk1, the kinase responsible for phosphorylating eIF4E. Structure-guided surface mutagenesis and protein-protein interaction assays were used to identify binding sites for eIF4A and Mnk1 within the HEAT-repeats of 4G/C. p97/DAP5, a translational modulator homologous to eIF4G, lacks an eIF4A binding site in the corresponding region. The second atypical HEAT domain of the 4G/C binds Mnk1 using two conserved aromatic/acidic-box (AA-box) motifs. Within the first AA-box, the aromatic residues contribute to the hydrophobic core of the domain, while the acidic residues form a negatively charged surface feature suitable for electrostatic interactions with basic residues in Mnk1.
KW - RNA
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U2 - https://doi.org/10.1016/j.str.2006.03.012
DO - https://doi.org/10.1016/j.str.2006.03.012
M3 - Article
C2 - 16698552
SN - 0969-2126
VL - 14
SP - 913
EP - 923
JO - Structure
JF - Structure
IS - 5
ER -