6C08

Zebrafish SLC38A9 with arginine bound in the cytosol open state

Summary for 6C08

• Entry DOI: 10.2210/pdb6c08/pdb
• Descriptor: antibody Fab Heavy Chain, antibody Fab light chain, Sodium-coupled neutral amino acid transporter 9, ... (4 entities in total)
• Functional Keywords: transporter, conformational state, substrate binding, complex, membrane protein
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 6
• Total formula weight: 200621.13

Authors

Lei, H.-T.,Gonen, T. (deposition date: 2017-12-28, release date: 2018-06-20, Last modification date: 2024-10-30)

Primary citation

Lei, H.T.,Ma, J.,Sanchez Martinez, S.,Gonen, T.
Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state.
Nat. Struct. Mol. Biol., 25:522-527, 2018

PubMed Abstract: 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.

PubMed: 29872228
DOI: 10.1038/s41594-018-0072-2

Experimental method

X-RAY DIFFRACTION (3.17 Å)