View source for 8dhu


==Crystal structure of LARP-DM15 from Drosophila melanogaster bound to m7GpppC==
<StructureSection load='8dhu' size='340' side='right'caption='[[8dhu]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dhu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DHU 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]] 2.295&#8491;</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=8dhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dhu OCA], [https://pdbe.org/8dhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dhu RCSB], [https://www.ebi.ac.uk/pdbsum/8dhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dhu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LARP_DROME LARP_DROME] RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability. Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:17951964, PubMed:19631203, PubMed:30772175, PubMed:35413237). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression. Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:35413237).<ref>PMID:17951964</ref> <ref>PMID:19631203</ref> <ref>PMID:30772175</ref> <ref>PMID:35413237</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
TOR (target of rapamycin), a ubiquitous protein kinase central to cellular homeostasis maintenance, fundamentally regulates ribosome biogenesis in part by its target La-related protein 1 (LARP1). Among other target transcripts, LARP1 specifically binds TOP (terminal oligopyrimidine) mRNAs encoding all 80 ribosomal proteins in a TOR-dependent manner through its C-terminal region containing the DM15 module. Though the functional implications of the LARP1 interaction with target mRNAs is controversial, it is clear that the TOP-LARP1-TOR axis is critical to cellular health in humans. Its existence and role in evolutionarily divergent animals remain less understood. We focused our work on expanding our knowledge of the first arm of the axis: the connection between LARP1-DM15 and the 5' TOP motif. We show that the overall DM15 architecture observed in humans is conserved in fruit fly and zebrafish. Both adopt familiar curved arrangements of HEAT-like repeats that bind 5' TOP mRNAs on the same conserved surface, although molecular dynamics simulations suggest that the N-terminal fold of the fruit fly DM15 is predicted to be unstable and unfold. We demonstrate that each ortholog interacts with TOP sequences with varying affinities. Importantly, we determine that the ability of the DM15 region to bind some TOP sequences but not others might amount to the context of the RNA structure, rather than the ability of the module to recognize some sequences but not others. We propose that TOP mRNAs may retain similar secondary structures to regulate LARP1 DM15 recognition.

Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution.,Nguyen E, Sosa JA, Cassidy KC, Berman AJ PLoS One. 2024 Aug 27;19(8):e0308574. doi: 10.1371/journal.pone.0308574. , eCollection 2024. PMID:39190712<ref>PMID:39190712</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dhu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Berman AJ]]
[[Category: Nguyen E]]