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6c08

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Zebrafish SLC38A9 with arginine bound in the cytosol open state

Structural highlights

6c08 is a 6 chain structure with sequence from Danio rerio and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.17Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lei HT, Ma J, Sanchez Martinez S, Gonen T. Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state. Nat Struct Mol Biol. 2018 Jun;25(6):522-527. doi: 10.1038/s41594-018-0072-2. Epub, 2018 Jun 5. PMID:29872228 doi:http://dx.doi.org/10.1038/s41594-018-0072-2