7KGV

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

7KGV の概要

• エントリーDOI: 10.2210/pdb7kgv/pdb
• 分子名称: Sodium-coupled neutral amino acid transporter 9, Monoclonal antibody Fab heavy chain, Monoclonal antibody Fab light chain (3 entities in total)
• 機能のキーワード: slc38a9, membrane protein, transport protein
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 215953.39

構造登録者

Lei, H.,Mu, X.,Hattne, J.,Gonen, T. (登録日: 2020-10-19, 公開日: 2020-12-23, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.4 Å)