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| | <StructureSection load='4zc4' size='340' side='right'caption='[[4zc4]], [[Resolution|resolution]] 1.86Å' scene=''> | | <StructureSection load='4zc4' size='340' side='right'caption='[[4zc4]], [[Resolution|resolution]] 1.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zc4]] is a 4 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=4ZC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZC4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zc4]] is a 4 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=4ZC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZC4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4zc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zc4 OCA], [https://pdbe.org/4zc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zc4 RCSB], [https://www.ebi.ac.uk/pdbsum/4zc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zc4 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=4zc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zc4 OCA], [http://pdbe.org/4zc4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zc4 RCSB], [http://www.ebi.ac.uk/pdbsum/4zc4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zc4 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Berman, A J]] | + | [[Category: Berman AJ]] |
| - | [[Category: Lahr, R M]] | + | [[Category: Lahr RM]] |
| - | [[Category: Heat-like]]
| + | |
| - | [[Category: Helical repeat]]
| + | |
| - | [[Category: Mrna]]
| + | |
| - | [[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
La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 A resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.
The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence.,Lahr RM, Mack SM, Heroux A, Blagden SP, Bousquet-Antonelli C, Deragon JM, Berman AJ Nucleic Acids Res. 2015 Jul 22. pii: gkv748. PMID:26206669[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, Mack SM, Heroux A, Blagden SP, Bousquet-Antonelli C, Deragon JM, Berman AJ. The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence. Nucleic Acids Res. 2015 Jul 22. pii: gkv748. PMID:26206669 doi:http://dx.doi.org/10.1093/nar/gkv748
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