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==LARP1 DM15 FYRE (F844Y, R847E) mutant bound to m7GpppG dinucleotide (capG)==
<StructureSection load='6pw3' size='340' side='right'caption='[[6pw3]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pw3]] 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=6PW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PW3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTG:7-METHYL-GUANOSINE-5-TRIPHOSPHATE-5-GUANOSINE'>GTG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6pw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pw3 OCA], [https://pdbe.org/6pw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pw3 RCSB], [https://www.ebi.ac.uk/pdbsum/6pw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pw3 ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== Publication Abstract from PubMed ==
The RNA-binding protein La-related protein 1 (LARP1) plays a central role in ribosome biosynthesis. Its C-terminal DM15 region binds the 7-methylguanosine (m(7)G) cap and 5' terminal oligopyrimidine (TOP) motif characteristic of transcripts encoding ribosomal proteins and translation factors. Under the control of mammalian target of rapamycin complex 1 (mTORC1), LARP1 regulates translation of these transcripts. Characterizing the dynamics of DM15-TOP recognition is essential to understanding this fundamental biological process. We use molecular dynamics simulations, biophysical assays, and X-ray crystallography to reveal the mechanism of DM15 binding to TOP transcripts. Residues C-terminal to the m(7)G-binding site play important roles in cap recognition. Furthermore, we show that the unusually static pocket that recognizes the +1 cytosine characteristic of TOP transcripts drives binding specificity. Finally, we demonstrate that the DM15 pockets involved in TOP-specific m(7)GpppC-motif recognition are likely druggable. Collectively, these studies suggest unique opportunities for further pharmacological development.

Capturing the Mechanism Underlying TOP mRNA Binding to LARP1.,Cassidy KC, Lahr RM, Kaminsky JC, Mack S, Fonseca BD, Das SR, Berman AJ, Durrant JD Structure. 2019 Oct 29. pii: S0969-2126(19)30347-8. doi:, 10.1016/j.str.2019.10.006. PMID:31676287<ref>PMID:31676287</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6pw3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Berman AJ]]
[[Category: Lahr RM]]