EIF1

Last updated
EIF1
Protein EIF1 PDB 2if1.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases EIF1 , A121, EIF-1, EIF1A, ISO1, SUI1, eukaryotic translation initiation factor 1, Eukaryotic initiation factor 1
External IDs HomoloGene: 130538 GeneCards: EIF1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005801

n/a

RefSeq (protein)

NP_005792

n/a

Location (UCSC) Chr 17: 41.69 – 41.69 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

Eukaryotic translation initiation factor 1 (eIF1) is a protein that in humans is encoded by the EIF1 gene. It is related to yeast SUI1. [3] [4] [5]

Contents

eIF1 interacts with the eukaryotic small (40S) ribosomal subunit and eIF3, and is a component of the 43S preinitiation complex (PIC). [6] eIF1 and eIF1A bind cooperatively to the 40S to stabilize an "open" conformation of the preinitiation complex (PIC) during eukaryotic translation initiation. [6] eIF1 binds to a region near the ribosomal A-site in the 40S subunit and functions in a manner similar to the structurally related bacterial counterpart IF1. [7]

Structure

eIF1 is a conserved translation protein in all eukaryotic cells that is responsible for the investigation of codon-anticodon mismatches during the initiation of translation. In order to determine the structure of human eIF1, an experiment with N-terminal His tag and eIF1 are conducted via using NMR spectroscopy. Scientists have discovered a binding site by generating yeast mutation and study the neighbor conserved residues located in the same region. GST pull-down experiments has shown that eIF1 binds precisely to the p110 subunit of eIF3 as a result explaining eIF1 recruiting. [8]

Function

The function of eIf1 has some hidden aspects. However, in all eukaryotic cells initiation of mRNA translation starts with scanning via ribosomal 43S preinitiation complexes starting from the 5’ end of the mRNA. Next, induction via eIF1 and eIF1A are needed to disclose the conformation of the 40S subunit in order to induce DEAD-box RNA helicase eIF4A, its cofactor eIF4B, and eIF4G activity. [9]    

See also

Related Research Articles

Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: gene translation, elongation, termination, and recapping.

Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNAiMet called the 43S preinitiation complex. Additional factors of the eIF4F complex recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex, followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the greater biological complexity of eukaryotic translation. There are at least twelve eukaryotic initiation factors, composed of many more polypeptides, and these are described below.

EIF4G2

Eukaryotic translation initiation factor 4 gamma 2 is a protein that in humans is encoded by the EIF4G2 gene.

EIF6

Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene.

EIF2S2

Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.

EIF2S3 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 2 subunit 3 (eIF2γ) is a protein that in humans is encoded by the EIF2S3 gene.

<span class="mw-page-title-main">EIF4A1</span> Protein coding gene in Humans

Eukaryotic initiation factor 4A-I is a 46 kDa cytosolic protein that, in humans, is encoded by the EIF4A1 gene, which is located on chromosome 17. It is the most prevalent member of the eIF4A family of ATP-dependant RNA helicases, and plays a critical role in the initiation of cap-dependent eukaryotic protein translation as a component of the eIF4F translation initiation complex. eIF4A1 unwinds the secondary structure of RNA within the 5'-UTR of mRNA, a critical step necessary for the recruitment of the 43S preinitiation complex, and thus the translation of protein in eukaryotes. It was first characterized in 1982 by Grifo, et al., who purified it from rabbit reticulocyte lysate.

EIF3B Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 3 subunit B (eIF3b) is a protein that in humans is encoded by the EIF3B gene.

EIF5 Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 5 is a protein that in humans is encoded by the EIF5 gene.

EIF1AX Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 1A, X-chromosomal (eIF1A) is a protein that in humans is encoded by the EIF1AX gene. This gene encodes an essential eukaryotic translation initiation factor. The protein is a component of the 43S pre-initiation complex (PIC), which mediates the recruitment of the small 40S ribosomal subunit to the 5' cap of messenger RNAs.

EIF3EIP

Eukaryotic translation initiation factor 3 subunit L (eIF3l), less commonly known as EIF3EIP, is a protein that in humans is encoded by the EIF3L gene.

EIF3D

Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a protein that in humans is encoded by the EIF3D gene.

EIF3K Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 3 subunit K (eIF3k) is a protein that in humans is encoded by the EIF3K gene.

EIF1AY Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 1A, Y-chromosomal is a protein that in humans is encoded by the EIF1AY gene.

Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human EIF4G1 has been the focus of extensive studies.

Eukaryotic Initiation Factor 2 (eIF2) is a eukaryotic initiation factor. It is required for most forms of eukaryotic translation initiation. eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner. eIF2 is a heterotrimer consisting of an alpha, a beta, and a gamma subunit.

The eukaryotic initiation factor-4A (eIF4A) family consists of 3 closely related proteins EIF4A1, EIF4A2, and EIF4A3. These factors are required for the binding of mRNA to 40S ribosomal subunits. In addition these proteins are helicases that function to unwind double-stranded RNA.

Eukaryotic initiation factor 3

Eukaryotic initiation factor 3 (eIF3) is a multiprotein complex that functions during the initiation phase of eukaryotic translation. It is essential for most forms of cap-dependent and cap-independent translation initiation. In humans, eIF3 consists of 13 nonidentical subunits (eIF3a-m) with a combined molecular weight of ~800 kDa, making it the largest translation initiation factor. The eIF3 complex is broadly conserved across eukaryotes, but the conservation of individual subunits varies across organisms. For instance, while most mammalian eIF3 complexes are composed of 13 subunits, budding yeast's eIF3 has only six subunits.

The 43S preinitiation complex 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).

DHX29

DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000173812 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Fields C, Adams MD (January 1994). "Expressed sequence tags identify a human isolog of the suil translation initiation factor". Biochemical and Biophysical Research Communications. 198 (1): 288–91. doi:10.1006/bbrc.1994.1040. PMID   7904817.
  4. Sheikh MS, Fernandez-Salas E, Yu M, Hussain A, Dinman JD, Peltz SW, Huang Y, Fornace AJ (June 1999). "Cloning and characterization of a human genotoxic and endoplasmic reticulum stress-inducible cDNA that encodes translation initiation factor 1(eIF1(A121/SUI1))". The Journal of Biological Chemistry. 274 (23): 16487–93. doi: 10.1074/jbc.274.23.16487 . PMID   10347211.
  5. "Entrez Gene: EIF1 eukaryotic translation initiation factor 1".
  6. 1 2 Aitken CE, Lorsch JR (June 2012). "A mechanistic overview of translation initiation in eukaryotes". Nature Structural & Molecular Biology. 19 (6): 568–76. doi:10.1038/nsmb.2303. PMID   22664984. S2CID   9201095.
  7. Fraser CS (July 2015). "Quantitative studies of mRNA recruitment to the eukaryotic ribosome". Biochimie. 114: 58–71. doi:10.1016/j.biochi.2015.02.017. PMC   4458453 . PMID   25742741.
  8. Fletcher CM, Pestova TV, Hellen CU, Wagner G (May 1999). "Structure and interactions of the translation initiation factor eIF1". The EMBO Journal. 18 (9): 2631–7. doi:10.1093/emboj/18.9.2631. PMC   1171342 . PMID   10228174.
  9. Jackson RJ, Hellen CU, Pestova TV (February 2010). "The mechanism of eukaryotic translation initiation and principles of its regulation". Nature Reviews. Molecular Cell Biology. 11 (2): 113–27. doi:10.1038/nrm2838. PMC   4461372 . PMID   20094052.
  10. "EIF1 - Eukaryotic translation initiation factor 1 - Homo sapiens (Human) - EIF1 gene & protein". www.uniprot.org. Retrieved 2018-09-23.

Further reading