43S preinitiation complex
The 43S preinitiation complex (43S PIC) is a ribonucleoprotein complex that exists during an early step of eukaryotic translation initiation. The 43S PIC contains the small ribosomal subunit (40S) bound by the initiation factors eIF1, eIF1A, eIF3, and the eIF2-Met-tRNAiMet-GTP ternary complex (eIF2-TC).{{cite journal | last1=Sonenberg | first1=Nahum | last2=Hinnebusch | first2=Alan G. | title=Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets | journal=Cell | publisher=Elsevier BV | volume=136 | issue=4 | year=2009 | issn=0092-8674 | doi=10.1016/j.cell.2009.01.042 | pmid=19239892 | pmc=3610329 | pages=731–745}}{{cite journal|last1=Aitken|first1=Colin E.|last2=Lorsch|first2=Jon R.|title=A mechanistic overview of translation initiation in eukaryotes|journal=Nat. Struct. Mol. Biol.|date=2012|volume=19|issue=6|pages=568–576|doi=10.1038/nsmb.2303|pmid=22664984|s2cid=9201095}}{{cite journal | last=Fraser | first=Christopher S. | title=Quantitative studies of mRNA recruitment to the eukaryotic ribosome | journal=Biochimie | publisher=Elsevier BV | volume=114 | year=2015 | issn=0300-9084 | doi=10.1016/j.biochi.2015.02.017 | pmid=25742741 | pages=58–71| pmc=4458453 }}{{cite journal | last=Hinnebusch | first=Alan G. | title=Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation | journal=Trends in Biochemical Sciences | publisher=Elsevier BV | volume=42 | issue=8 | year=2017 | issn=0968-0004 | doi=10.1016/j.tibs.2017.03.004 | pmid=28442192 | pages=589–611}}
Function
The 43S is an important intermediate complex during cap-dependent translation initiation. In the canonical model of translation initiation, the 43S PIC is pre-formed as a stable complex and recruited to the 5' cap of eukaryotic messenger RNAs (mRNAs) by the eIF4F complex.{{cite journal | last1=Sokabe | first1=Masaaki | last2=Fraser | first2=Christopher S. | title=Human Eukaryotic Initiation Factor 2 (eIF2)-GTP-Met-tRNAiTernary Complex and eIF3 Stabilize the 43 S Preinitiation Complex | journal=Journal of Biological Chemistry | publisher=American Society for Biochemistry & Molecular Biology (ASBMB) | volume=289 | issue=46 | date=2014-09-22 | issn=0021-9258 | doi=10.1074/jbc.m114.602870 | pmid=25246524 | pages=31827–31836| pmc=4231660 | doi-access=free }} The 43S PIC then "scans" in the 5' --> 3' direction along the mRNA in an ATP-dependent fashion (via eIF4A and/or other RNA helicases such as Ded1/DDX3 and DHX29) to locate the start codon. Start codon recognition occurs through base-pairing between the Met-tRNAiMet and AUG in the ribosomal P-site and a number of associated changes, and is followed by joining of the large 60S ribosomal subunit to form the 80S ribosome.
Structure
Due to its size and complexity, the 43S PIC has eluded high resolution structural characterization. However, combined approaches including cryo-EM, cross-linking, and the structural characterization of individual components, has led to models for the complex organization.{{cite journal | last1=Hashem | first1=Yaser | last2=des Georges | first2=Amedee | last3=Dhote | first3=Vidya | last4=Langlois | first4=Robert | last5=Liao | first5=Hstau Y. | last6=Grassucci | first6=Robert A. | last7=Hellen | first7=Christopher U.T. | last8=Pestova | first8=Tatyana V. | last9=Frank | first9=Joachim | title=Structure of the Mammalian Ribosomal 43S Preinitiation Complex Bound to the Scanning Factor DHX29 | journal=Cell | publisher=Elsevier BV | volume=153 | issue=5 | year=2013 | issn=0092-8674 | doi=10.1016/j.cell.2013.04.036 | pmid=23706745 | pmc=3730827 | pages=1108–1119}}{{cite journal | last1=Erzberger | first1=Jan P. | last2=Stengel | first2=Florian | last3=Pellarin | first3=Riccardo | last4=Zhang | first4=Suyang | last5=Schaefer | first5=Tanja | last6=Aylett | first6=Christopher H.S. | last7=Cimermančič | first7=Peter | last8=Boehringer | first8=Daniel | last9=Sali | first9=Andrej | last10=Aebersold | first10=Ruedi | last11=Ban | first11=Nenad | title=Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex | journal=Cell | publisher=Elsevier BV | volume=158 | issue=5 | year=2014 | issn=0092-8674 | doi=10.1016/j.cell.2014.07.044 | pmid=25171412 | pmc=4151992 | pages=1123–1135}}{{cite journal | last1=des Georges | first1=Amedee | last2=Dhote | first2=Vidya | last3=Kuhn | first3=Lauriane | last4=Hellen | first4=Christopher U. T. | last5=Pestova | first5=Tatyana V. | last6=Frank | first6=Joachim | last7=Hashem | first7=Yaser | title=Structure of mammalian eIF3 in the context of the 43S preinitiation complex | journal=Nature | publisher=Springer Nature | volume=525 | issue=7570 | date=2015-09-07 | issn=0028-0836 | doi=10.1038/nature14891 | pmid=26344199 | pmc=4719162 | pages=491–495| bibcode=2015Natur.525..491D }}
See also
References
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{{MolBioGeneExp}}
{{GeneticTranslation}}
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{{DEFAULTSORT:Eukaryotic Translation}}