8HIK

The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex

8HIK の概要

• エントリーDOI: 10.2210/pdb8hik/pdb
• EMDBエントリー: 34819
• 分子名称: BRIL-SLC19A1 chimera, Anti-BRIL Fab heavy chain, Anti-Fab nanobody, ... (5 entities in total)
• 機能のキーワード: slc19a1, rfc, transporter, folates, 5-mthf, tpp, transport protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 145544.02

構造登録者

Zhang, Z.,Dang, Y. (登録日: 2022-11-20, 公開日: 2022-12-21, 最終更新日: 2024-10-23)

主引用文献

Dang, Y.,Zhou, D.,Du, X.,Zhao, H.,Lee, C.H.,Yang, J.,Wang, Y.,Qin, C.,Guo, Z.,Zhang, Z.
Molecular mechanism of substrate recognition by folate transporter SLC19A1.
Cell Discov, 8:141-141, 2022

PubMed Abstract: Folate (vitamin B) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 remains unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 Å resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work establishes the molecular basis of substrate recognition by this central folate transporter.

PubMed: 36575193
DOI: 10.1038/s41421-022-00508-w

実験手法

ELECTRON MICROSCOPY (3.72 Å)