7BC6

Cryo-EM structure of the outward open proton coupled folate transporter at pH 7.5

7BC6 の概要

• エントリーDOI: 10.2210/pdb7bc6/pdb
• EMDBエントリー: 12140
• 分子名称: Proton-coupled folate transporter, nanobody (2 entities in total)
• 機能のキーワード: transporter folate proton symporter, membrane protein
• 由来する生物種: Gallus gallus (Chicken); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64826.58

構造登録者

Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (登録日: 2020-12-18, 公開日: 2021-05-12, 最終更新日: 2025-07-09)

主引用文献

Parker, J.L.,Deme, J.C.,Kuteyi, G.,Wu, Z.,Huo, J.,Goldman, I.D.,Owens, R.J.,Biggin, P.C.,Lea, S.M.,Newstead, S.
Structural basis of antifolate recognition and transport by PCFT.
Nature, 595:130-134, 2021

PubMed Abstract: Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine. Folate deficiency is associated with a number of developmental, immune and neurological disorders. Mammals cannot synthesize folates de novo; several systems have therefore evolved to take up folates from the diet and distribute them within the body. The proton-coupled folate transporter (PCFT) (also known as SLC46A1) mediates folate uptake across the intestinal brush border membrane and the choroid plexus, and is an important route for the delivery of antifolate drugs in cancer chemotherapy. How PCFT recognizes folates or antifolate agents is currently unclear. Here we present cryo-electron microscopy structures of PCFT in a substrate-free state and in complex with a new-generation antifolate drug (pemetrexed). Our results provide a structural basis for understanding antifolate recognition and provide insights into the pH-regulated mechanism of folate transport mediated by PCFT.

PubMed: 34040256
DOI: 10.1038/s41586-021-03579-z

実験手法

ELECTRON MICROSCOPY (3.2 Å)