6pw3: Difference between revisions

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New page: '''Unreleased structure''' The entry 6pw3 is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 6pw3 is ON HOLD
==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>
<div style="background-color:#fffaf0;">
== 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.


Authors:  
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>


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