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| | ==Crystal structure of LARP1-unique domain DM15 bound to m7GpppC== | | ==Crystal structure of LARP1-unique domain DM15 bound to m7GpppC== |
| - | <StructureSection load='5v87' size='340' side='right' caption='[[5v87]], [[Resolution|resolution]] 1.69Å' scene=''> | + | <StructureSection load='5v87' size='340' side='right'caption='[[5v87]], [[Resolution|resolution]] 1.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v87]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V87 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V87 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v87]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V87 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V87 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=91P:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-AZANYL-7-METHYL-6-OXIDANYLIDENE-1~{H}-PURIN-9-IUM-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+[[(2~{R},3~{S},4~{R},5~{R})-5-(4-AZANYL-2-OXIDANYLIDENE-PYRIMIDIN-1-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+HYDROGEN+PHOSPHATE'>91P</scene>, <scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.692Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v7c|5v7c]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91P:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-AZANYL-7-METHYL-6-OXIDANYLIDENE-1~{H}-PURIN-9-IUM-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+[[(2~{R},3~{S},4~{R},5~{R})-5-(4-AZANYL-2-OXIDANYLIDENE-PYRIMIDIN-1-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+HYDROGEN+PHOSPHATE'>91P</scene>, <scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LARP1, KIAA0731, LARP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5v87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v87 OCA], [https://pdbe.org/5v87 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v87 RCSB], [https://www.ebi.ac.uk/pdbsum/5v87 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v87 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v87 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v87 OCA], [http://pdbe.org/5v87 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v87 RCSB], [http://www.ebi.ac.uk/pdbsum/5v87 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v87 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LARP1_HUMAN LARP1_HUMAN]] RNA-binding protein that promotes translation of specific classes of mRNAs downstream of the mTORC1 complex. Associates with the mRNA 5'cap in an MTOR-dependent manner and associates with mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding for ribosomal proteins and several components of the translation machinery. Associates with actively translating ribosomes via interaction with PABPC1/PABP and stimulates translation of mRNAs containing a 5'TOP, thereby regulating cell growth and proliferation.<ref>PMID:20430826</ref> <ref>PMID:23711370</ref> <ref>PMID:24532714</ref> | + | [https://www.uniprot.org/uniprot/LARP1_HUMAN LARP1_HUMAN] RNA-binding protein that promotes translation of specific classes of mRNAs downstream of the mTORC1 complex. Associates with the mRNA 5'cap in an MTOR-dependent manner and associates with mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding for ribosomal proteins and several components of the translation machinery. Associates with actively translating ribosomes via interaction with PABPC1/PABP and stimulates translation of mRNAs containing a 5'TOP, thereby regulating cell growth and proliferation.<ref>PMID:20430826</ref> <ref>PMID:23711370</ref> <ref>PMID:24532714</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Berman, A J]] | + | [[Category: Large Structures]] |
| - | [[Category: Lahr, R M]] | + | [[Category: Berman AJ]] |
| - | [[Category: 5'top]] | + | [[Category: Lahr RM]] |
| - | [[Category: Cap-binding]]
| + | |
| - | [[Category: Dm15]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| Structural highlights
Function
LARP1_HUMAN RNA-binding protein that promotes translation of specific classes of mRNAs downstream of the mTORC1 complex. Associates with the mRNA 5'cap in an MTOR-dependent manner and associates with mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding for ribosomal proteins and several components of the translation machinery. Associates with actively translating ribosomes via interaction with PABPC1/PABP and stimulates translation of mRNAs containing a 5'TOP, thereby regulating cell growth and proliferation.[1] [2] [3]
Publication Abstract from PubMed
The 5'terminal oligopyrimidine (5'TOP) motif is a cis-regulatory RNA element located immediately downstream of the 7-methyl-guanosine [m7G] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (m7GTP), and a capped cytosine (m7GpppC) resolved to 2.6, 1.8 and 1.7 A, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.
La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs.,Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, Blagden SP, Alain T, Berman AJ Elife. 2017 Apr 5;6. pii: e24146. doi: 10.7554/eLife.24146. PMID:28379136[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Burrows C, Abd Latip N, Lam SJ, Carpenter L, Sawicka K, Tzolovsky G, Gabra H, Bushell M, Glover DM, Willis AE, Blagden SP. The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration. Nucleic Acids Res. 2010 Sep;38(16):5542-53. doi: 10.1093/nar/gkq294. Epub 2010, Apr 29. PMID:20430826 doi:http://dx.doi.org/10.1093/nar/gkq294
- ↑ Aoki K, Adachi S, Homoto M, Kusano H, Koike K, Natsume T. LARP1 specifically recognizes the 3' terminus of poly(A) mRNA. FEBS Lett. 2013 Jul 11;587(14):2173-8. doi: 10.1016/j.febslet.2013.05.035. Epub, 2013 May 24. PMID:23711370 doi:http://dx.doi.org/10.1016/j.febslet.2013.05.035
- ↑ Tcherkezian J, Cargnello M, Romeo Y, Huttlin EL, Lavoie G, Gygi SP, Roux PP. Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation. Genes Dev. 2014 Feb 15;28(4):357-71. doi: 10.1101/gad.231407.113. PMID:24532714 doi:http://dx.doi.org/10.1101/gad.231407.113
- ↑ Lahr RM, Fonseca BD, Ciotti GE, Al-Ashtal HA, Jia JJ, Niklaus MR, Blagden SP, Alain T, Berman AJ. La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs. Elife. 2017 Apr 5;6. pii: e24146. doi: 10.7554/eLife.24146. PMID:28379136 doi:http://dx.doi.org/10.7554/eLife.24146
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