8WNY

Cryo EM map of SLC7A10-SLC3A2 complex in the D-serine bound state

Summary for 8WNY

• Entry DOI: 10.2210/pdb8wny/pdb
• EMDB information: 37675
• Descriptor: Amino acid transporter heavy chain SLC3A2, Asc-type amino acid transporter 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: slc7a10, slc3a2, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 125992.11

Authors

Li, Y.N.,Guo, Y.Y.,Dai, L.,Yan, R.H. (deposition date: 2023-10-06, release date: 2024-05-15, Last modification date: 2024-11-06)

Primary citation

Li, Y.,Guo, Y.,Broer, A.,Dai, L.,Brӧer, S.,Yan, R.
Cryo-EM structure of the human Asc-1 transporter complex.
Nat Commun, 15:3036-3036, 2024

PubMed Abstract: The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex.

PubMed: 38589439
DOI: 10.1038/s41467-024-47468-1

Experimental method

ELECTRON MICROSCOPY (3.5 Å)