View source for 43S preinitiation complex

'''The 43S preinitiation complex''' ('''43S PIC''') is a [[Ribonucleoprotein|ribonucleoprotein complex]] that exists during an early step of [[eukaryotic translation]] initiation. The 43S PIC contains the [[Eukaryotic small ribosomal subunit (40S)|small ribosomal subunit (40S)]] bound by the initiation factors [[eIF1]], [[eIF1AX|eIF1A]], [[eIF3]], and the [[eIF2]]-Met-[[tRNA]]<sub>i</sub><sup>Met</sup>-GTP ternary complex (eIF2-TC).<ref name="Sonenberg Hinnebusch 2009 pp. 731–745">{{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}}</ref><ref name="Aitken">{{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}}</ref><ref name="Fraser 2015 pp. 58–71">{{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 }}</ref><ref name="Hinnebusch 2017 pp. 589–611">{{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}}</ref>

==Function==
The 43S is an important intermediate complex during [[Eukaryotic translation#Cap-dependent initiation|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 [[Five-prime cap|5' cap]] of eukaryotic [[messenger RNA]]s (mRNAs) by the [[eIF4F]] complex.<ref name="Aitken"/><ref name="Fraser 2015 pp. 58–71"/><ref name="Sokabe Fraser pp. 31827–31836">{{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 }}</ref> The 43S PIC then "scans" in the 5' --> 3' direction along the mRNA in an ATP-dependent fashion (via [[eIF4A]] and/or other RNA [[helicase]]s such as [[DDX3X|Ded1/DDX3]] and [[DHX29]]) to locate the start codon. Start codon recognition occurs through base-pairing between the Met-tRNA<sub>i</sub><sup>Met</sup> and AUG in the ribosomal [[P-site]] and a number of associated changes, and is followed by joining of the [[Eukaryotic large ribosomal subunit (60S)|large 60S ribosomal subunit]] to form the [[Eukaryotic ribosome (80S)|80S ribosome]].

==Structure==
Due to its size and complexity, the 43S PIC has eluded high resolution structural characterization. However, combined approaches including [[Cryo-electron microscopy|cryo-EM]], [[cross-link]]ing, and the structural characterization of individual components, has led to models for the complex organization.<ref name="Hashem des Georges Dhote Langlois 2013 pp. 1108–1119">{{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}}</ref><ref name="Erzberger Stengel Pellarin Zhang 2014 pp. 1123–1135">{{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}}</ref><ref name="des Georges Dhote Kuhn Hellen pp. 491–495">{{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 }}</ref>

== See also ==
*[[Eukaryotic translation]]
*[[Eukaryotic small ribosomal subunit (40S)|40S ribosomal subunit]]
*[[eIF3]]

==References==
{{reflist}}

{{MolBioGeneExp}}
{{GeneticTranslation}}
{{Portal bar|Biology|border=no}}

{{DEFAULTSORT:Eukaryotic Translation}}
<!--- Categories --->
[[Category:Molecular biology]]
[[Category:Gene expression]]
[[Category:RNA-binding proteins]]
[[Category:Protein biosynthesis]]
[[Category:Protein complexes]]