EIF1 — Mediated Wiki

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Eukaryotic translation initiation factor 1 (eIF1)''' is a protein that in humans is encoded by the ''EIF1'' gene. It is related to yeast SUI1.<ref name="Fields_1994">{{cite journal | vauthors = Fields C, Adams MD | title = Expressed sequence tags identify a human isolog of the suil translation initiation factor | journal = Biochemical and Biophysical Research Communications | volume = 198 | issue = 1 | pages = 288–291 | date = January 1994 | pmid = 7904817 | doi = 10.1006/bbrc.1994.1040 | bibcode = 1994BBRC..198..288F }}</ref><ref name="Sheikh_1999">{{cite journal | vauthors = Sheikh MS, Fernandez-Salas E, Yu M, Hussain A, Dinman JD, Peltz SW, Huang Y, Fornace AJ | title = Cloning and characterization of a human genotoxic and endoplasmic reticulum stress-inducible cDNA that encodes translation initiation factor 1(eIF1(A121/SUI1)) | journal = The Journal of Biological Chemistry | volume = 274 | issue = 23 | pages = 16487–16493 | date = June 1999 | pmid = 10347211 | doi = 10.1074/jbc.274.23.16487 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: EIF1 eukaryotic translation initiation factor 1 | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10209 }}</ref>

eIF1 interacts with the eukaryotic small (40S) ribosomal subunit and eIF3, and is a component of the 43S preinitiation complex (PIC).<ref name="Aitken_2012">{{cite journal | vauthors = Aitken CE, Lorsch JR | title = A mechanistic overview of translation initiation in eukaryotes | journal = Nature Structural & Molecular Biology | volume = 19 | issue = 6 | pages = 568–576 | date = June 2012 | pmid = 22664984 | doi = 10.1038/nsmb.2303 | s2cid = 9201095 }}</ref> eIF1 and eIF1A bind cooperatively to the 40S to stabilize an "open" conformation of the preinitiation complex (PIC) during eukaryotic translation initiation.<ref name="Aitken_2012" /> eIF1 binds to a region near the ribosomal P-site in the 40S subunit and functions in a manner similar to the structurally related bacterial counterpart IF3.<ref name="Fraser_2015">{{cite journal | vauthors = Fraser CS | title = Quantitative studies of mRNA recruitment to the eukaryotic ribosome | journal = Biochimie | volume = 114 | pages = 58–71 | date = July 2015 | pmid = 25742741 | pmc = 4458453 | doi = 10.1016/j.biochi.2015.02.017 }}</ref>

== Structure == eIF1's structure was first determined in 1999 by solution-state NMR spectroscopy, which revealed that it consists of a five-stranded beta-sheet which is sided by two alpha-helices.<ref>{{cite journal | vauthors = Fletcher CM, Pestova TV, Hellen CU, Wagner G | title = Structure and interactions of the translation initiation factor eIF1 | journal = The EMBO Journal | volume = 18 | issue = 9 | pages = 2631–2637 | date = May 1999 | pmid = 10228174 | pmc = 1171342 | doi = 10.1093/emboj/18.9.2631 }}</ref> Crystallographic experiments showed that eIF1 is located at the P-site of the small ribosomal subunit, binding to the 18S rRNA with a basic surface.<ref>{{cite journal | vauthors = Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N | title = Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1 | journal = Science | volume = 331 | issue = 6018 | pages = 730–736 | date = February 2011 | pmid = 21205638 | doi = 10.1126/science.1198308 | hdl-access = free | bibcode = 2011Sci...331..730R | hdl = 20.500.11850/153130 }}</ref> To date, a number of cryo-EM structures have been solved that include eIF1 in the context of various translation initiation complexes.<ref>{{cite journal | vauthors = Petrychenko V, Yi SH, Liedtke D, Peng BZ, Rodnina MV, Fischer N | title = Structural basis for translational control by the human 48S initiation complex | journal = Nature Structural & Molecular Biology | volume = 32 | issue = 1 | pages = 62–72 | date = January 2025 | pmid = 39289545 | pmc = 11746136 | doi = 10.1038/s41594-024-01378-4 }}</ref><ref>{{cite journal | vauthors = Brito Querido J, Sokabe M, Díaz-López I, Gordiyenko Y, Zuber P, Du Y, Albacete-Albacete L, Ramakrishnan V, Fraser CS | title = Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit | journal = Nature Communications | volume = 15 | issue = 1 | date = August 2024 | pmid = 39117603 | pmc = 11310195 | doi = 10.1038/s41467-024-50672-8 | bibcode = 2024NatCo..15.6633B | article-number = 6633 }}</ref><ref>{{cite journal | vauthors = Villamayor-Belinchón L, Sharma P, Gordiyenko Y, Llácer JL, Hussain T | title = Structural basis of AUC codon discrimination during translation initiation in yeast | journal = Nucleic Acids Research | volume = 52 | issue = 18 | pages = 11317–11335 | date = October 2024 | pmid = 39193907 | pmc = 11472065 | doi = 10.1093/nar/gkae737 }}</ref>

== Function == In eukaryotic cells, translation initiation on an mRNA involves scanning of the mRNA by the 43S pre-initiation complex in search of the translation initiation start codon.<ref>{{cite journal | vauthors = Hinnebusch AG | title = Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation | journal = Trends in Biochemical Sciences | volume = 42 | issue = 8 | pages = 589–611 | date = August 2017 | pmid = 28442192 | doi = 10.1016/j.tibs.2017.03.004 }}</ref> Accurate identification of the start codon is very important, as other translation start sites may lead to the production of defect proteins. A codon is detected as a start codon by interaction with the tRNA's anticodon that is positioned in the P-site of the small ribosomal subunit, which leads to closing of the pre-initiation complex.<ref>{{cite journal | vauthors = Hussain T, Llácer JL, Fernández IS, Munoz A, Martin-Marcos P, Savva CG, Lorsch JR, Hinnebusch AG, Ramakrishnan V | title = Structural changes enable start codon recognition by the eukaryotic translation initiation complex | journal = Cell | volume = 159 | issue = 3 | pages = 597–607 | date = October 2014 | pmid = 25417110 | pmc = 4217140 | doi = 10.1016/j.cell.2014.10.001 }}</ref> eIF1 is positioned on the small ribosomal subunit such that it blocks the closure of the pre-initiation complex. It thereby aids in selecting the correct start codon, since only the correct codon-anticodon interaction provides enough energy to displace eIF1 and thus close the pre-initiation complex.<ref>{{cite journal | vauthors = Thakur A, Hinnebusch AG | title = eIF1 Loop 2 interactions with Met-tRNA<sub>i</sub> control the accuracy of start codon selection by the scanning preinitiation complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 18 | pages = E4159–E4168 | date = May 2018 | pmid = 29666249 | pmc = 5939108 | doi = 10.1073/pnas.1800938115 | doi-access = free | bibcode = 2018PNAS..115E4159T }}</ref>

== See also ==

* Eukaryotic initiation factors<ref>{{Cite web | title = EIF1 - Eukaryotic translation initiation factor 1 - Homo sapiens (Human) - EIF1 gene & protein | url = https://www.uniprot.org/uniprot/P41567 | website = www.uniprot.org | language = en | access-date = 2018-09-23 }}</ref> {{clear}} == References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Lian Z, Pan J, Liu J, Zhang S, Zhu M, Arbuthnot P, Kew M, Feitelson MA | title = The translation initiation factor, hu-Sui1 may be a target of hepatitis B X antigen in hepatocarcinogenesis | journal = Oncogene | volume = 18 | issue = 9 | pages = 1677–1687 | date = March 1999 | pmid = 10208429 | doi = 10.1038/sj.onc.1202470 | s2cid = 22809502 | doi-access = free }} * {{cite journal | vauthors = Chin LS, Singh SK, Wang Q, Murray SF | title = Identification of okadaic-acid-induced genes by mRNA differential display in glioma cells | journal = Journal of Biomedical Science | volume = 7 | issue = 2 | pages = 152–159 | year = 2000 | pmid = 10754390 | doi = 10.1007/BF02256622 }} * {{cite journal | vauthors = Mendell JT, Medghalchi SM, Lake RG, Noensie EN, Dietz HC | title = Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes | journal = Molecular and Cellular Biology | volume = 20 | issue = 23 | pages = 8944–8957 | date = December 2000 | pmid = 11073994 | pmc = 86549 | doi = 10.1128/MCB.20.23.8944-8957.2000 }} * {{cite journal | vauthors = Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ | title = Immunoaffinity profiling of tyrosine phosphorylation in cancer cells | journal = Nature Biotechnology | volume = 23 | issue = 1 | pages = 94–101 | date = January 2005 | pmid = 15592455 | doi = 10.1038/nbt1046 | s2cid = 7200157 }} {{refend}}

== External links == * {{UCSC genome browser|EIF1}} * {{UCSC gene details|EIF1}} * [http://www.nature.com/nrmicro/journal/v5/n1/box/nrmicro1558_BX1.html Cap-dependent translation initiation] from Nature Reviews Microbiology. A good image and overview of the function of initiation factors * {{PDBe-KB2|P41567|Eukaryotic translation initiation factor 1}}