7KGV

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

Summary for 7KGV

• Entry DOI: 10.2210/pdb7kgv/pdb
• Descriptor: Sodium-coupled neutral amino acid transporter 9, Monoclonal antibody Fab heavy chain, Monoclonal antibody Fab light chain (3 entities in total)
• Functional Keywords: slc38a9, membrane protein, transport protein
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 6
• Total formula weight: 215953.39

Authors

Lei, H.,Mu, X.,Hattne, J.,Gonen, T. (deposition date: 2020-10-19, release date: 2020-12-23, Last modification date: 2024-10-23)

Primary citation

Lei, H.T.,Mu, X.,Hattne, J.,Gonen, T.
A conformational change in the N terminus of SLC38A9 signals mTORC1 activation.
Structure, 29:426-, 2021

PubMed Abstract: 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.

PubMed: 33296665
DOI: 10.1016/j.str.2020.11.014

Experimental method

X-RAY DIFFRACTION (3.4 Å)