6c08: Difference between revisions
New page: '''Unreleased structure''' The entry 6c08 is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Zebrafish SLC38A9 with arginine bound in the cytosol open state== | ||
<StructureSection load='6c08' size='340' side='right'caption='[[6c08]], [[Resolution|resolution]] 3.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c08]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C08 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]] 3.17Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</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=6c08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c08 OCA], [https://pdbe.org/6c08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c08 RCSB], [https://www.ebi.ac.uk/pdbsum/6c08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c08 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/S38A9_DANRE S38A9_DANRE] Lysosomal amino acid transporter involved in the control of mTORC1 activity in response to amino acids. Probably acts as a amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes 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. Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Mediates transport of amino acids with low capacity, suggesting that it acts as an amino acid sensor instead.[UniProtKB:Q8NBW4] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recent advances in understanding intracellular amino acid transport and mechanistic target of rapamycin complex 1 (mTORC1) signaling shed light on solute carrier 38, family A member 9 (SLC38A9), a lysosomal transporter responsible for the binding and translocation of several essential amino acids. Here we present the first crystal structure of SLC38A9 from Danio rerio in complex with arginine. As captured in the cytosol-open state, the bound arginine was locked in a transitional state stabilized by transmembrane helix 1 (TM1) of drSLC38A9, which was anchored at the groove between TM5 and TM7. These anchoring interactions were mediated by the highly conserved WNTMM motif in TM1, and mutations in this motif abolished arginine transport by drSLC38A9. The underlying mechanism of substrate binding is critical for sensitizing the mTORC1 signaling pathway to amino acids and for maintenance of lysosomal amino acid homeostasis. This study offers a first glimpse into a prototypical model for SLC38 transporters. | |||
Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state.,Lei HT, Ma J, Sanchez Martinez S, Gonen T Nat Struct Mol Biol. 2018 Jun;25(6):522-527. doi: 10.1038/s41594-018-0072-2. Epub, 2018 Jun 5. PMID:29872228<ref>PMID:29872228</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6c08" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Gonen T]] | |||
[[Category: Lei H-T]] | |||
Latest revision as of 14:04, 30 October 2024
Zebrafish SLC38A9 with arginine bound in the cytosol open stateZebrafish SLC38A9 with arginine bound in the cytosol open state
Structural highlights
FunctionS38A9_DANRE Lysosomal amino acid transporter involved in the control of mTORC1 activity in response to amino acids. Probably acts as a amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes 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. Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Mediates transport of amino acids with low capacity, suggesting that it acts as an amino acid sensor instead.[UniProtKB:Q8NBW4] Publication Abstract from PubMedRecent advances in understanding intracellular amino acid transport and mechanistic target of rapamycin complex 1 (mTORC1) signaling shed light on solute carrier 38, family A member 9 (SLC38A9), a lysosomal transporter responsible for the binding and translocation of several essential amino acids. Here we present the first crystal structure of SLC38A9 from Danio rerio in complex with arginine. As captured in the cytosol-open state, the bound arginine was locked in a transitional state stabilized by transmembrane helix 1 (TM1) of drSLC38A9, which was anchored at the groove between TM5 and TM7. These anchoring interactions were mediated by the highly conserved WNTMM motif in TM1, and mutations in this motif abolished arginine transport by drSLC38A9. The underlying mechanism of substrate binding is critical for sensitizing the mTORC1 signaling pathway to amino acids and for maintenance of lysosomal amino acid homeostasis. This study offers a first glimpse into a prototypical model for SLC38 transporters. Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state.,Lei HT, Ma J, Sanchez Martinez S, Gonen T Nat Struct Mol Biol. 2018 Jun;25(6):522-527. doi: 10.1038/s41594-018-0072-2. Epub, 2018 Jun 5. PMID:29872228[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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