@article {56203,
	title = {Structural basis for substrate binding and specificity of a sodium-alanine symporter AgcS.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {116},
	year = {2019},
	month = {2019 Jan 18},
	pages = {2086-90},
	abstract = {<p>The amino acid, polyamine, and organocation (APC) superfamily is the second largest superfamily of membrane proteins forming secondary transporters that move a range of organic molecules across the cell membrane. Each transporter in the APC superfamily is specific for a unique subset of substrates, even if they possess a similar structural fold. The mechanism of substrate selectivity remains, by and large, elusive. Here, we report two crystal structures of an APC member from , the alanine or glycine:cation symporter (AgcS), with l- or d-alanine bound. Structural analysis combined with site-directed mutagenesis and functional studies inform on substrate binding, specificity, and modulation of the AgcS family and reveal key structural features that allow this transporter to accommodate glycine and alanine while excluding all other amino acids. Mutation of key residues in the substrate binding site expand the selectivity to include valine and leucine. These studies provide initial insights into substrate selectivity in AgcS symporters.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1806206116},
	author = {Ma, Jinming and Lei, Hsiang-Ting and Reyes, Francis E and Sanchez-Martinez, Silvia and Sarhan, Maen F and Hattne, Johan and Gonen, Tamir}
}
@article {49264,
	title = {Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state.},
	journal = {Nature Structural \& Molecular Biology},
	volume = {25},
	year = {2018},
	month = {2018 Jun},
	pages = {522-527},
	abstract = {<p>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.</p>
},
	issn = {1545-9985},
	doi = {10.1038/s41594-018-0072-2},
	author = {Lei, Hsiang-Ting and Ma, Jinming and Sanchez Martinez, Silvia and Gonen, Tamir}
}
