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TitleConformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex.
Journal, issue, pagesMol Cell, Vol. 59, Issue 3, Page 399-412, Year 2015
Publish dateAug 6, 2015
AuthorsJose L Llácer / Tanweer Hussain / Laura Marler / Colin Echeverría Aitken / Anil Thakur / Jon R Lorsch / Alan G Hinnebusch / V Ramakrishnan /
PubMed AbstractTranslation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and ...Translation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.0 Å and 4.9 Å, respectively. These reconstructions show eIF2β as well as a configuration of eIF3 that appears to encircle the 40S, occupying part of the subunit interface. Comparison of the complexes reveals a large conformational change in the 40S head from an open mRNA latch conformation to a closed one that constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus elucidating key events in start codon recognition.
External linksMol Cell / PubMed:26212456 / PubMed Central
MethodsEM (single particle)
Resolution3.46 - 14.9 Å
Structure data

EMDB-3047: 40S-eIF1A-eIF1 complex
PDB-3jam: CryoEM structure of 40S-eIF1A-eIF1 complex from yeast
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-3048, PDB-3jap:
Structure of a partial yeast 48S preinitiation complex in closed conformation
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-3049:
Structure of a partial yeast 48S preinitiation complex in open conformation
Method: EM (single particle) / Resolution: 6.0 Å

EMDB-3050:
Structure of a partial yeast 43S preinitiation complex
Method: EM (single particle) / Resolution: 14.9 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-MET:
METHIONINE

ChemComp-GCP:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-PCP, energy-carrying molecule analogue*YM

Source
  • kluyveromyces lactis (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
  • synthetic construct (others)
KeywordsTRANSLATION / Eukaryotic translation initiation / 48S / small ribosome subunit / 40S / 43S

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