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Yeast eIF1Yeast eIF1
IntroductionIntroduction
Translation is an essential process for both prokaryotes and eukaryotes to make various proteins from nucleic acid. It requires three different steps: initiation, elongation, and termination. Many proteins are needed in the initiation phase to form an initiation complex with the ribosome and promote the translation. In eukaryotes, these proteins are also known as eukaryotic initiation factors (eIF). The eIFs were first studied through the genetic analyzed of yeast Saccharomyces cerevisiae [1]. The initiation process is complex since it involves at least 12 eIFs containing more than 30 polypeptides , including eIF1, eIF2, eIF3, eIF4, and eIF5 [1].
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| 2ogh, 20 NMR models () | |||||||||
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| Gene: | SUI1, RFR1 (Saccharomyces cerevisiae) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
StructureStructure
eIF1 is a small protein (12 kDa) that is encode by sui1 which is one of the component of multifactor complex (MFC) that plays an important role in regulating translation initiation [2][3]. eIF1 is a universal translation factor across organisms which make eIF1 homologs can be found in other eukayotes, archaea, and some bacteria [4]. Yeast eIF1 contains a on one side with N-terminal tail (aa 1-23) or NTT [2]. It is homolog to since the structure is similar to human eIF1 (87%) with 63% matched identity (DNA composition) [2] [4]. However, yeast eIF1 has two different conformations with two clear sets of backbone resonances for 13 of the 20 residues that lead to 20 different possible solution structure of yeast eIF1 [2].
eIF1-ribosome binding siteeIF1-ribosome binding site
eIF1 would bind to the ribosomal 40S, in its P-site region, which would affect the conformation of the 40S subunit and the position of mRNA and the start codon initiation [5]. Surprisingly, this binding site region is similar to the binding site of prokaryotic initiation factor IF3 to the ribosome, despite their unrelated structure [5]. Together with eIF1A, eIF5, eIF3, and the eIF2.GTP.Met-tRNAiMet ternary complex (TC), eIF1 would form a 43S preinitiation complex (PIC) [2][5][6].
eIF1-eIF5 binding siteseIF1-eIF5 binding sites
There are two : at the NTT site of eIF1 and at a KH surface area, a specific region that rich in Lysine (K) and hydrophobic (H) residues [2]. These bindings are different from the eIF1-ribosome binding site and are salt dependent, with high salt concentration would make the interaction weaker [2]. The eIF1-NTT area is believed to play role in stimulating the MFC assembly by promoting the eIF5- eIF2β [2]. The other binding site area (eIF1-KH) is believed to play role in the AUG start codon selection in translation initiation [2].
Function and MechanismFunction and Mechanism
eIF1 is essential to control the ribosome conformational rearrangement prior to initiation translation by controlling the start codon selection and promoting the formation of MFC [2][3].
AUG Start Codon SelectionAUG Start Codon Selection
stimulates the recruitment of TC to the 40s subunit
- how it is released after AUG recognition?
Multifactor Complex AssemblyMultifactor Complex Assembly
MutationsMutations
eIF1-eIF5eIF1-eIF5
at the eIF1-eIF5 binding site
- altering the basic part of eIF1-KH
- altering the hydrophobic residues of eIF1
ReferencesReferences
- ↑ 1.0 1.1 1.2 Maduzia LL, Moreau A, Poullet N, Chaffre S, Zhang Y. The role of eIF1 in translation initiation codon selection in Caenorhabditis elegans. Genetics. 2010 Dec;186(4):1187-96. Epub 2010 Sep 20. PMID:20855569 doi:10.1534/genetics.110.121541
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Reibarkh M, Yamamoto Y, Singh CR, del Rio F, Fahmy A, Lee B, Luna RE, Ii M, Wagner G, Asano K. Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection. J Biol Chem. 2008 Jan 11;283(2):1094-103. Epub 2007 Nov 1. PMID:17974565 doi:10.1074/jbc.M708155200
- ↑ 3.0 3.1 3.2 Asano K, Sachs MS. Translation factor control of ribosome conformation during start codon selection. Genes Dev. 2007 Jun 1;21(11):1280-7. PMID:17545463 doi:10.1101/gad.1562707
- ↑ 4.0 4.1 4.2 Fletcher CM, Pestova TV, Hellen CU, Wagner G. Structure and interactions of the translation initiation factor eIF1. EMBO J. 1999 May 4;18(9):2631-7. PMID:10228174 doi:10.1093/emboj/18.9.2631
- ↑ 5.0 5.1 5.2 5.3 Lomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes Dev. 2003 Nov 15;17(22):2786-97. Epub 2003 Nov 4. PMID:14600024 doi:10.1101/gad.1141803
- ↑ 6.0 6.1 Cheung YN, Maag D, Mitchell SF, Fekete CA, Algire MA, Takacs JE, Shirokikh N, Pestova T, Lorsch JR, Hinnebusch AG. Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo. Genes Dev. 2007 May 15;21(10):1217-30. PMID:17504939 doi:10.1101/gad.1528307