8HII

The BRIL-SLC19A1/Fab/Nb ternary complex

Summary for 8HII

• Entry DOI: 10.2210/pdb8hii/pdb
• EMDB information: 34817
• Descriptor: BRIL-SLC19A1 chimera, anti-BRIL Fab heavy chain, anti-Fab nanobody, ... (4 entities in total)
• Functional Keywords: slc19a1, rfc, transporter, folates, bril, transport protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 145118.71

Authors

Zhang, Z.,Dang, Y. (deposition date: 2022-11-20, release date: 2022-12-21, Last modification date: 2023-01-11)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.57 Å)