6ybt

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Structure of a human 48S translational initiation complex - eIF3bgi

Structural highlights

6ybt is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EIF3A_HUMAN RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632, PubMed:11169732). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815).[HAMAP-Rule:MF_03000][1] [2] [3] [4] (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634).[5] [6] (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426).[7]

Publication Abstract from PubMed

A key step in translational initiation is the recruitment of the 43S preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48S initiation complex (i.e., the 48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo-electron microscopy to determine the structure of a reconstituted human 48S The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43S The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests that downstream mRNA is unwound at least in part by being "pulled" through the 40S subunit during scanning.

Structure of a human 48S translational initiation complex.,Brito Querido J, Sokabe M, Kraatz S, Gordiyenko Y, Skehel JM, Fraser CS, Ramakrishnan V Science. 2020 Sep 4;369(6508):1220-1227. doi: 10.1126/science.aba4904. PMID:32883864[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
12 reviews cite this structure
Control of the eIF4E activity: structural insights and pharmacological implications.
Romagnoli et al. (2021)
11 more
63 other articles
No citations found

See Also

References

  1. ↑ Lin L, Holbro T, Alonso G, Gerosa D, Burger MM. Molecular interaction between human tumor marker protein p150, the largest subunit of eIF3, and intermediate filament protein K7. J Cell Biochem. 2001;80(4):483-90. PMID:11169732 doi:<483::aid-jcb1002>3.0.co;2-b 10.1002/1097-4644(20010315)80:4<483::aid-jcb1002>3.0.co;2-b
  2. ↑ Masutani M, Sonenberg N, Yokoyama S, Imataka H. Reconstitution reveals the functional core of mammalian eIF3. EMBO J. 2007 Jul 25;26(14):3373-83. doi: 10.1038/sj.emboj.7601765. Epub 2007 Jun , 21. PMID:17581632 doi:http://dx.doi.org/10.1038/sj.emboj.7601765
  3. ↑ Lee AS, Kranzusch PJ, Cate JH. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature. 2015 Jun 4;522(7554):111-4. doi: 10.1038/nature14267. Epub 2015 Apr 6. PMID:25849773 doi:http://dx.doi.org/10.1038/nature14267
  4. ↑ Lee AS, Kranzusch PJ, Doudna JA, Cate JH. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016 Aug 4;536(7614):96-9. PMID:27462815 doi:http://dx.doi.org/10.1038/nature18954
  5. ↑ Sun C, Querol-Audí J, Mortimer SA, Arias-Palomo E, Doudna JA, Nogales E, Cate JH. Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation. Nucleic Acids Res. 2013 Aug;41(15):7512-21. PMID:23766293 doi:10.1093/nar/gkt510
  6. ↑ Sweeney TR, Abaeva IS, Pestova TV, Hellen CU. The mechanism of translation initiation on Type 1 picornavirus IRESs. EMBO J. 2014 Jan 7;33(1):76-92. PMID:24357634 doi:10.1002/embj.201386124
  7. ↑ Poyry TA, Kaminski A, Connell EJ, Fraser CS, Jackson RJ. The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation. Genes Dev. 2007 Dec 1;21(23):3149-62. doi: 10.1101/gad.439507. PMID:18056426 doi:http://dx.doi.org/10.1101/gad.439507
  8. ↑ Brito Querido J, Sokabe M, Kraatz S, Gordiyenko Y, Skehel JM, Fraser CS, Ramakrishnan V. Structure of a human 48S translational initiation complex. Science. 2020 Sep 4;369(6508):1220-1227. doi: 10.1126/science.aba4904. PMID:32883864 doi:http://dx.doi.org/10.1126/science.aba4904

Contents


PDB ID 6ybt

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