Eukaryotic initiation factor: Difference between revisions

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load='1dq8' size='350' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''
<StructureSection load='' size='350' side='right' scene='50/507723/Cv/1' caption='Human initiation factor EIF4E complex with 7-methyl GPPPA [[1ipb]]'>
== Function ==


'''Eukaryotic initiation factors''' or '''Eukaryotic translation initiation factors''' (EIF) are involved in the initiation of protein translation.  They form a complex with the small subunit of the ribosome and Met-tRNA which scans the mRNA and recognizes the initiation codon AUG<ref>PMID:16449648</ref>.


   
*'''EIF1''' is implicated in the stringency of start codon selection<ref>PMID:28541577</ref>. <br />
*'''EIF2''' binds GTP and Met-tRNA and transfers Met-tRNA to the ribosomal 40S subunit<ref>PMID:10216940</ref>. <br />
*'''EIF3''' attaches to the 5'-terminal regions mRNA and scan along it to the initiation codon<ref>PMID:26344199</ref>. <br />
*'''EIF4''' recognizes the m7GpppN cap structure at the 5'-terminal of mRNA<ref>PMID:18443631</ref>. For details see [[C-terminal portion of human eIF4GI]].<br />
*'''EIF5''' is implicated in the stringency of start codon selection<ref>PMID:25114053</ref>. <br />
*'''EIF6''' is involved in maturation and/or export from the nucleus of the 60S ribosomal subunit<ref>PMID:16814427</ref>. <br />


'''Eukaryotic initiation factors''' (EIF) are involved in the initiation of protein translation.  They form a complex with the small subunit of the ribosome and Met-tRNA which scans the mRNA and recognizes the initiation codon AUG.
== Disease ==


==3D structures of eukaryotic initiation factor==
Overexpression of individual subunits of eIF3 may cause malignant transformation <ref>PMID:25450521</ref>.  Overexpression of eIF4g is implicated in breast cancer.


===EIF1===
== Structural insights ==


[[2if1]], [[1d7q]] – hEIF1 – human – NMR<BR />
EIF domains include the N terminal domain (NTD), C terminal domain (CTD), RNA recognition domain, middle domain, PAZ domain of EIF2C and a protein-protein interaction domain (PCI) of EIF3.
[[2ogh]] - yEIF1 – NMR<BR />


===EIF2===
*<scene name='50/507723/Cv/4'>P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE (7-methyl GPPPA) binding site</scene>. Water molecules shown as red spheres.


[[1kl9]] – hEIF2A<BR />
==3D structures of eukaryotic initiation factor==  
[[1q8x ]]– hEIF2A - NMR<BR />
[[Eukaryotic initiation factor 3D structures]]  
[[1si2]], [[1si3]], [[4ei3]], [[4f3t]] – hEIF2C PAZ domain + DNA<BR />
[[3luk]] - hEIF2C MID domain <BR />
[[3lud]], [[3lug]], [[3luh]], [[3luj]], [[3qx8]], [[3qx9]] - hEIF2C MID domain + nucleotide<br />
[[1q46]] – yEIF2A – yeast<BR />
[[2a19]], [[2a1a]] – yEIF2A (mutant) + interferon-induced protein kinase<BR />
[[3ecs]] – hEIF2B
 
===EIF3===
 
[[2nlw]] - hEIF3B RNA recognition domain – NMR<BR />
[[3ns5]], [[3ns6]] - yEIF3B RNA recognition domain<BR />
[[2krb]] - hEIF3B RNA recognition domain + hEIF3J peptide<br />
[[2cq0]] – hEIF3G RNA recognition domain – NMR<BR />
[[3zwl]] - yEIF3I + EIF3B C terminal<BR />
[[3bpj]] – hEIF3J<BR />
[[1rz4]] – hEIF3K
 
===EIF4===
 
[[1fuk]] – yEIF4A C terminal<BR />
[[1fuu]] - yEIF4A mRNA helicase domain<BR />
[[2g9n]], [[3bor]] – hEIF4A DEAD domain<BR />
[[3ex7]], [[2xb2]]  – hEIF4A + MAGO homolog + RNA-binding protein 8A + CASC3 + RNA<BR />
[[2zu6]], [[3eiq]] – hEIF4A + programmed cell death protein<BR />
[[1wi8]], [[2j76]] – hEIF4B RNA recognition domain - NMR<BR />
[[1ejh]] – mEIF4E + EIF4G peptide + GDP – mouse<BR />
[[1ej1]], [[1l8b]] - mEIF4E + nucleotide<br />
[[2gpq]], [[3tf2]] – hEIF4E<BR />
[[2wmc]] - EIF4E - pea<BR />
[[2idr]] – wEIF4E – wheat<BR />
[[2idv]] - wEIF4E (mutant) + GDP<BR />
[[1ipb]], [[1ipc]] - hEIF4E + nucleotide<br />
[[4dt6]], [[4dum]] – hEIF4E + inhibitor<BR />
[[2w97]] – hEIF4E + hEIF4G peptide<br />
[[1wkw]] - hEIF4E + EIF4E-binding protein peptide + GDP<BR />
[[2v8w]], [[2v8x]], [[2v8y]], [[3u7x]] - hEIF4E + EIF4E-binding protein peptide<br />
[[3am7]] - hEIF4E + EIF4E-binding protein peptide + nucleotide<br />
[[1ej4]] - mEIF4E + EIF4E-binding protein peptide<br />
[[3hxg]], [[3hxi]] - EIF4E + EIF4E-binding protein peptide + GDP – ''Schistosoma mansoni''<BR />
[[3m93]], [[3m94]] - EIF4E + EIF4E-binding protein peptide + nucleotide – Pig roundworm<BR />
[[1ap8]] – yEIF4E + GDP – NMR<BR />
[[1rf8]] - yEIF4E + yEIF4GI peptide + GDP<BR />
[[2vso]], [[2vsx]] - yEIF4E + yEIF4F<BR />
[[3l6a]] - hEIF4GII C terminal<BR />
[[1ug3]] – hEIF4GI C terminal (mutant) <BR />
[[1hu3]], [[3d3m]] – hEIF4GII middle domain<BR />
[[2dng]] – hEIF4H RNA recognition domain – NMR<BR />
 
===EIF5===
 
[[1eif]], [[2eif]] – EIF5A – ''Methanocaldococcus janaschii''<BR />
[[1x6o]] – EIF5A – ''Leishmania braziliensis''<BR />
[[1xtd]] - EIF5A – ''Leishmania mexicana''<BR />
[[3hks]] – EIF5A – ''Arabidopsis thaliana''<BR />
[[3cpf]] - hEIF<BR />
[[2ful]] – yEIF5 C terminal<BR />
[[2iu1]] - hEIF5 C terminal<BR />
[[2g2k]] – hEIF5 N terminal (mutant) – NMR<BR />
[[2e9h]] – hEIF5 – NMR<BR />
[[3cpf]] – hEIF5A<BR />
[[3er0]] - yEIF5A


===EIF6===
</StructureSection>


[[1g62]] – yEIF6 <BR />
== References ==
[[2x7n]] – yEIF6S + sarcin-ricin loop + ribosomal protein L23 + ribosomal protein L24
<references/>
[[Category:Topic Page]]

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Michal Harel, Alexander Berchansky, Joel L. Sussman