@article{babafa9929274d989a23884df2a1242b,
title = "The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome",
abstract = "Initiation of translation is the process by which initiator tRNA and the start codon of mRNA are positioned in the ribosomal P site. In eukaryotes, one of the first steps involves the binding of two small factors, eIF1 and eIF1A, to the small (40S) ribosomal subunit. This facilitates tRNA binding, allows scanning of mRNA, and maintains fidelity of start codon recognition. Using cryo-EM, we have obtained 3D reconstructions of 40S bound to both eIF1 and eIF1A, and with each factor alone. These structures reveal that together, eIF1 and eIF1A stabilize a conformational change that opens the mRNA binding channel. Biochemical data reveal that both factors accelerate the rate of ternary complex (eIF2•GTP•Met-tRNAiMet) binding to 40S but only eIF1A stabilizes this interaction. Our results suggest that eIF1 and eIF1A promote an open, scanning-competent preinitiation complex that closes upon start codon recognition and eIF1 release to stabilize ternary complex binding and clamp down on mRNA.",
keywords = "RNA",
author = "Passmore, {Lori A.} and Schmeing, {T. Martin} and David Maag and Applefield, {Drew J.} and Acker, {Michael G.} and Algire, {Mikkel A A.} and Lorsch, {Jon R.} and V. Ramakrishnan",
note = "Funding Information: We thank Richard Henderson for valuable discussions, advice on electron microscopy, and comments on the manuscript. We are grateful to Joachim Frank for providing a 15 {\AA} cryo-EM map of the yeast 40S subunit and Shaoxia Chen, Alan Roseman, Peter Rosenthal, Jude Short, and Steve Ludtke for assistance with EM and image processing. We also thank Albert Weixlbaumer for useful discussions, Frank Murphy for providing a script to evaluate and sort data, and Junjie Zhang for providing EMAN scripts to calculate variance maps. This work was supported by the Medical Research Council (UK), the Agouron Institute and National Institute of Health grants GM67624 (to V.R.) and GM62128 (to J.R.L.). L.A.P. is a Beit Memorial Research Fellow, and T.M.S. was supported by a fellowship from EMBO and is funded by a Human Frontiers Science Program Organization long term fellowship. ",
year = "2007",
month = apr,
day = "13",
doi = "10.1016/j.molcel.2007.03.018",
language = "English (US)",
volume = "26",
pages = "41--50",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}