View source for 6ehp


==The crystal structure of the human LAMTOR complex==
<StructureSection load='6ehp' size='340' side='right'caption='[[6ehp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ehp]] is a 5 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=6EHP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EHP 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6ehp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ehp OCA], [https://pdbe.org/6ehp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ehp RCSB], [https://www.ebi.ac.uk/pdbsum/6ehp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ehp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LTOR1_HUMAN LTOR1_HUMAN] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.<ref>PMID:19654316</ref> <ref>PMID:20381137</ref> <ref>PMID:20544018</ref> <ref>PMID:22980980</ref> 
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== Publication Abstract from PubMed ==
LAMTOR (Late endosomal and lysosomal adaptor and mitogen activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) activator) also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag GTPases associated with the pentamer through their C-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the impact of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.

Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling.,de Araujo MEG, Naschberger A, Furnrohr BG, Stasyk T, Dunzendorfer-Matt T, Lechner S, Welti S, Kremser L, Shivalingaiah G, Offterdinger M, Lindner HH, Huber LA, Scheffzek K Science. 2017 Sep 21. pii: eaao1583. doi: 10.1126/science.aao1583. PMID:28935770<ref>PMID:28935770</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 6ehp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ragulator complex 3D structures|Ragulator complex 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Naschberger A]]
[[Category: Scheffzek K]]