Structural Changes Enable Start Codon Recognition by the Eukaryotic Translation Initiation Complex

被引：162

作者：

Hussain, Tanweer ^{[1
]}

Llacer, Jose L. ^{[1
]}

Fernandez, Israel S. ^{[1
]}

Munoz, Antonio ^{[2
,4
]}

Martin-Marcos, Pilar ^{[3
]}

Savva, Christos G. ^{[1
]}

Lorsch, Jon R. ^{[2
,4
]}

Hinnebusch, Alan G. ^{[3
]}

Ramakrishnan, V. ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[2] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[3] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA

[4] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Mech & Regulat Prot Synth, NIH, Bethesda, MD 20892 USA

来源：

CELL | 2014年 / 159卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

40S RIBOSOMAL-SUBUNIT; C-TERMINAL DOMAIN; PREINITIATION COMPLEX; CRYSTAL-STRUCTURE; FUNCTIONAL INTERACTIONS; MESSENGER-RNA; FACTORS EIF1; SELECTION; BINDING; TRNA(MET);

D O I：

10.1016/j.cell.2014.10.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

During eukaryotic translation initiation, initiator tRNA does not insert fully into the P decoding site on the 40S ribosomal subunit. This conformation (POUT) is compatible with scanning mRNA for the AUG start codon. Base pairing with AUG is thought to promote isomerization to a more stable conformation (PIN) that arrests scanning and promotes dissociation of eIF1 from the 40S subunit. Here, we present a cryoEM reconstruction of a yeast preinitiation complex at 4.0 angstrom resolution with initiator tRNA in the PIN state, prior to eIF1 release. The structure reveals stabilization of the codon-anticodon duplex by the N-terminal tail of eIF1A, changes in the structure of eIF1 likely instrumental in its subsequent release, and changes in the conformation of eIF2. The mRNA traverses the entire mRNA cleft and makes connections to the regulatory domain of eIF2 alpha, eIF1A, and ribosomal elements that allow recognition of context nucleotides surrounding the AUG codon.

引用

页码：597 / 607

页数：11

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