3j8c

Model of the human eIF3 PCI-MPN octamer docked into the 43S EM mapModel of the human eIF3 PCI-MPN octamer docked into the 43S EM map

3j8c, resolution 11.60Å

Structural highlights

3j8c is a 8 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3j7k. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 11.6Å
Experimental data:	Check
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]

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[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

[1]

[2]

[3]

[4]

[5]

[6]

[7]