8WNY

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

8WNY の概要

• エントリーDOI: 10.2210/pdb8wny/pdb
• EMDBエントリー: 37675
• 分子名称: Amino acid transporter heavy chain SLC3A2, Asc-type amino acid transporter 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: slc7a10, slc3a2, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 125992.11

構造登録者

Li, Y.N.,Guo, Y.Y.,Dai, L.,Yan, R.H. (登録日: 2023-10-06, 公開日: 2024-05-15, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.5 Å)