7kgv | pdb_00007kgv

Crystal structure of sodium-coupled neutral amino acid transporter SLC38A9 in the N-terminal plugged form

spinqualitylabelsall models 7kgv, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7kgv 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 3.4Å 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 mTORC1 is a central hub that integrates environmental cues, such as cellular stresses and nutrient availability to modulate metabolism and cellular responses. Recently, SLC38A9, a lysosomal amino acid transporter, emerged as a sensor for luminal arginine and as an activator of mTORC1. The amino acid-mediated activation of mTORC1 is regulated by the N-terminal domain of SLC38A9. Here, we determined the crystal structure of zebrafish SLC38A9 (drSLC38A9) and found the N-terminal fragment inserted deep within the transporter, bound in the substrate-binding pocket where normally arginine would bind. This represents a significant conformational change of the N-terminal domain (N-plug) when compared with our recent arginine-bound structure of drSLC38A9. We propose a ball-and-chain model for mTORC1 activation, where N-plug insertion and Rag GTPase binding with SLC38A9 is regulated by luminal arginine levels. This work provides important insights into nutrient sensing by SLC38A9 to activate the mTORC1 pathways in response to dietary amino acids. A conformational change in the N terminus of SLC38A9 signals mTORC1 activation.,Lei HT, Mu X, Hattne J, Gonen T Structure. 2021 May 6;29(5):426-432.e8. doi: 10.1016/j.str.2020.11.014. Epub 2020 , Dec 8. PMID:33296665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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