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| <StructureSection load='6yan' size='340' side='right'caption='[[6yan]], [[Resolution|resolution]] 3.48Å' scene=''> | | <StructureSection load='6yan' size='340' side='right'caption='[[6yan]], [[Resolution|resolution]] 3.48Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[6yan]] is a 39 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YAN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YAN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yan]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YAN FirstGlance]. <br> |
- | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=C4J:'>C4J</scene>, <scene name='pdbligand=T6A:N-[N-(9-B-D-RIBOFURANOSYLPURIN-6-YL)CARBAMOYL]THREONINE-5-MONOPHOSPHATE'>T6A</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.48Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6yal|6yal]], [[6yam|6yam]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C4J:(2~{S})-2-azanyl-4-[5-[(2~{S},3~{R},4~{S},5~{S})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]-3-methyl-2,6-bis(oxidanylidene)pyrimidin-1-yl]butanoic+acid'>C4J</scene>, <scene name='pdbligand=T6A:N-[N-(9-B-D-RIBOFURANOSYLPURIN-6-YL)CARBAMOYL]THREONINE-5-MONOPHOSPHATE'>T6A</scene></td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yan OCA], [http://pdbe.org/6yan PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yan RCSB], [http://www.ebi.ac.uk/pdbsum/6yan PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yan ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yan OCA], [https://pdbe.org/6yan PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yan RCSB], [https://www.ebi.ac.uk/pdbsum/6yan PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yan ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/G1TLT8_RABIT G1TLT8_RABIT]] Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA.[HAMAP-Rule:MF_03016] [[http://www.uniprot.org/uniprot/G1TN72_RABIT G1TN72_RABIT]] May play a role during erythropoiesis through regulation of transcription factor DDIT3 (By similarity).[HAMAP-Rule:MF_03122] | + | [https://www.uniprot.org/uniprot/RS3_RABIT RS3_RABIT] Component of the small ribosomal subunit (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). Has endonuclease activity and plays a role in repair of damaged DNA (By similarity). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (By similarity). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (By similarity). Has also been shown to bind with similar affinity to intact and damaged DNA (By similarity). Stimulates the N-glycosylase activity of the base excision protein OGG1 (By similarity). Enhances the uracil excision activity of UNG1 (By similarity). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (By similarity). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (By similarity). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (By similarity). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (By similarity). Represses its own translation by binding to its cognate mRNA (By similarity). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (By similarity). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (By similarity). Involved in induction of apoptosis through its role in activation of CASP8 (By similarity). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (By similarity). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (By similarity).[UniProtKB:P23396]<ref>PMID:23873042</ref> <ref>PMID:25601755</ref> <ref>PMID:26245381</ref> <ref>PMID:27863242</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| </div> | | </div> |
| <div class="pdbe-citations 6yan" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6yan" style="background-color:#fffaf0;"></div> |
| + | |
| + | ==See Also== |
| + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| + | *[[Ribosome 3D structures|Ribosome 3D structures]] |
| + | *[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
- | [[Category: Bochler, A]] | + | [[Category: Bochler A]] |
- | [[Category: Guca, E]] | + | [[Category: Guca E]] |
- | [[Category: Hashem, Y]] | + | [[Category: Hashem Y]] |
- | [[Category: Simonetti, A]] | + | [[Category: Simonetti A]] |
- | [[Category: Eukaryotic initiation factor 1a]]
| + | |
- | [[Category: Initiation complex]]
| + | |
- | [[Category: Rabbit]]
| + | |
- | [[Category: Translation]]
| + | |
| Structural highlights
Function
RS3_RABIT Component of the small ribosomal subunit (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). Has endonuclease activity and plays a role in repair of damaged DNA (By similarity). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (By similarity). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (By similarity). Has also been shown to bind with similar affinity to intact and damaged DNA (By similarity). Stimulates the N-glycosylase activity of the base excision protein OGG1 (By similarity). Enhances the uracil excision activity of UNG1 (By similarity). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (By similarity). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (By similarity). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (By similarity). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (By similarity). Represses its own translation by binding to its cognate mRNA (By similarity). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (By similarity). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (By similarity). Involved in induction of apoptosis through its role in activation of CASP8 (By similarity). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (By similarity). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (By similarity).[UniProtKB:P23396][1] [2] [3] [4]
Publication Abstract from PubMed
In higher eukaryotes, the mRNA sequence in the direct vicinity of the start codon, called the Kozak sequence (CRCCaugG, where R is a purine), is known to influence the rate of the initiation process. However, the molecular basis underlying its role remains poorly understood. Here, we present the cryoelectron microscopy (cryo-EM) structures of mammalian late-stage 48S initiation complexes (LS48S ICs) in the presence of two different native mRNA sequences, beta-globin and histone 4, at overall resolution of 3 and 3.5 A, respectively. Our high-resolution structures unravel key interactions from the mRNA to eukaryotic initiation factors (eIFs): 1A, 2, 3, 18S rRNA, and several 40S ribosomal proteins. In addition, we are able to study the structural role of ABCE1 in the formation of native 48S ICs. Our results reveal a comprehensive map of ribosome/eIF-mRNA and ribosome/eIF-tRNA interactions and suggest the impact of mRNA sequence on the structure of the LS48S IC.
Structural Insights into the Mammalian Late-Stage Initiation Complexes.,Simonetti A, Guca E, Bochler A, Kuhn L, Hashem Y Cell Rep. 2020 Apr 7;31(1):107497. doi: 10.1016/j.celrep.2020.03.061. PMID:32268096[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature. 2013 Jul 21. doi: 10.1038/nature12355. PMID:23873042 doi:10.1038/nature12355
- ↑ Muhs M, Hilal T, Mielke T, Skabkin MA, Sanbonmatsu KY, Pestova TV, Spahn CM. Cryo-EM of Ribosomal 80S Complexes with Termination Factors Reveals the Translocated Cricket Paralysis Virus IRES. Mol Cell. 2015 Feb 5;57(3):422-432. doi: 10.1016/j.molcel.2014.12.016. Epub 2015 , Jan 15. PMID:25601755 doi:http://dx.doi.org/10.1016/j.molcel.2014.12.016
- ↑ Brown A, Shao S, Murray J, Hegde RS, Ramakrishnan V. Structural basis for stop codon recognition in eukaryotes. Nature. 2015 Aug 27;524(7566):493-6. doi: 10.1038/nature14896. Epub 2015 Aug 5. PMID:26245381 doi:http://dx.doi.org/10.1038/nature14896
- ↑ Shao S, Murray J, Brown A, Taunton J, Ramakrishnan V, Hegde RS. Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes. Cell. 2016 Nov 17;167(5):1229-1240.e15. doi: 10.1016/j.cell.2016.10.046. PMID:27863242 doi:http://dx.doi.org/10.1016/j.cell.2016.10.046
- ↑ Simonetti A, Guca E, Bochler A, Kuhn L, Hashem Y. Structural Insights into the Mammalian Late-Stage Initiation Complexes. Cell Rep. 2020 Apr 7;31(1):107497. doi: 10.1016/j.celrep.2020.03.061. PMID:32268096 doi:http://dx.doi.org/10.1016/j.celrep.2020.03.061
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