|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Solution structure of the La motif of human LARP6== | | ==Solution structure of the La motif of human LARP6== |
| - | <StructureSection load='2mtf' size='340' side='right'caption='[[2mtf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mtf' size='340' side='right'caption='[[2mtf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mtf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MTF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mtf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MTF FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LARP6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mtf OCA], [https://pdbe.org/2mtf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mtf RCSB], [https://www.ebi.ac.uk/pdbsum/2mtf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mtf 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=2mtf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mtf OCA], [https://pdbe.org/2mtf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mtf RCSB], [https://www.ebi.ac.uk/pdbsum/2mtf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mtf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/LARP6_HUMAN LARP6_HUMAN]] Regulates the coordinated translation of type I collagen alpha-1 and alpha-2 mRNAs, CO1A1 and CO1A2. Stabilizes mRNAs through high-affinity binding of a stem-loop structure in their 5' UTR. This regulation requires VIM and MYH10 filaments, and the helicase DHX9.<ref>PMID:20603131</ref> <ref>PMID:21746880</ref> <ref>PMID:22190748</ref>
| + | [https://www.uniprot.org/uniprot/LARP6_HUMAN LARP6_HUMAN] Regulates the coordinated translation of type I collagen alpha-1 and alpha-2 mRNAs, CO1A1 and CO1A2. Stabilizes mRNAs through high-affinity binding of a stem-loop structure in their 5' UTR. This regulation requires VIM and MYH10 filaments, and the helicase DHX9.<ref>PMID:20603131</ref> <ref>PMID:21746880</ref> <ref>PMID:22190748</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Atkinson, A R]] | + | [[Category: Atkinson AR]] |
| - | [[Category: Conte, M R]] | + | [[Category: Conte MR]] |
| - | [[Category: Kelly, G]] | + | [[Category: Kelly G]] |
| - | [[Category: Martino, L]] | + | [[Category: Martino L]] |
| - | [[Category: Salisbury, N JH]] | + | [[Category: Salisbury NJH]] |
| - | [[Category: Acheron]]
| + | |
| - | [[Category: La motif]]
| + | |
| - | [[Category: La-related protein]]
| + | |
| - | [[Category: Larp]]
| + | |
| - | [[Category: Larp6]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
LARP6_HUMAN Regulates the coordinated translation of type I collagen alpha-1 and alpha-2 mRNAs, CO1A1 and CO1A2. Stabilizes mRNAs through high-affinity binding of a stem-loop structure in their 5' UTR. This regulation requires VIM and MYH10 filaments, and the helicase DHX9.[1] [2] [3]
Publication Abstract from PubMed
The La-related proteins (LARPs) form a diverse group of RNA-binding proteins characterized by the possession of a composite RNA binding unit, the La module. The La module comprises two domains, the La motif (LaM) and the RRM1, which together recognize and bind to a wide array of RNA substrates. Structural information regarding the La module is at present restricted to the prototypic La protein, which acts as an RNA chaperone binding to 3' UUUOH sequences of nascent RNA polymerase III transcripts. In contrast, LARP6 is implicated in the regulation of collagen synthesis and interacts with a specific stem-loop within the 5' UTR of the collagen mRNA. Here, we present the structure of the LaM and RRM1 of human LARP6 uncovering in both cases considerable structural variation in comparison to the equivalent domains in La and revealing an unprecedented fold for the RRM1. A mutagenic study guided by the structures revealed that RNA recognition requires synergy between the LaM and RRM1 as well as the participation of the interdomain linker, probably in realizing tandem domain configurations and dynamics required for substrate selectivity. Our study highlights a considerable complexity and plasticity in the architecture of the La module within LARPs.
Synergic interplay of the La motif, RRM1 and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module.,Martino L, Pennell S, Kelly G, Busi B, Brown P, Atkinson RA, Salisbury NJ, Ooi ZH, See KW, Smerdon SJ, Alfano C, Bui TT, Conte MR Nucleic Acids Res. 2014 Dec 8. pii: gku1287. PMID:25488812[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cai L, Fritz D, Stefanovic L, Stefanovic B. Nonmuscle myosin-dependent synthesis of type I collagen. J Mol Biol. 2010 Aug 27;401(4):564-78. doi: 10.1016/j.jmb.2010.06.057. Epub 2010 , Jul 13. PMID:20603131 doi:http://dx.doi.org/10.1016/j.jmb.2010.06.057
- ↑ Challa AA, Stefanovic B. A novel role of vimentin filaments: binding and stabilization of collagen mRNAs. Mol Cell Biol. 2011 Sep;31(18):3773-89. doi: 10.1128/MCB.05263-11. Epub 2011 Jul , 11. PMID:21746880 doi:10.1128/MCB.05263-11
- ↑ Manojlovic Z, Stefanovic B. A novel role of RNA helicase A in regulation of translation of type I collagen mRNAs. RNA. 2012 Feb;18(2):321-34. doi: 10.1261/rna.030288.111. Epub 2011 Dec 21. PMID:22190748 doi:http://dx.doi.org/10.1261/rna.030288.111
- ↑ Martino L, Pennell S, Kelly G, Busi B, Brown P, Atkinson RA, Salisbury NJ, Ooi ZH, See KW, Smerdon SJ, Alfano C, Bui TT, Conte MR. Synergic interplay of the La motif, RRM1 and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module. Nucleic Acids Res. 2014 Dec 8. pii: gku1287. PMID:25488812 doi:http://dx.doi.org/10.1093/nar/gku1287
|
