5NIV

Crystal structure of 5D3 Fab

5NIV の概要

• エントリーDOI: 10.2210/pdb5niv/pdb
• 分子名称: Light chain of 5D3 Fab, Heavy chain of 5D3 Fab (3 entities in total)
• 機能のキーワード: fab, abcg2, inhibitor, immune system
• 由来する生物種: Mus musculus (House mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47219.42

構造登録者

Manolaridis, I.,Locher, K.P. (登録日: 2017-03-27, 公開日: 2017-06-07, 最終更新日: 2024-01-17)

主引用文献

Taylor, N.M.I.,Manolaridis, I.,Jackson, S.M.,Kowal, J.,Stahlberg, H.,Locher, K.P.
Structure of the human multidrug transporter ABCG2.
Nature, 546:504-509, 2017

PubMed Abstract: ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of human ABCG2 determined by cryo-electron microscopy, providing the first high-resolution insight into a human multidrug transporter. We visualize ABCG2 in complex with two antigen-binding fragments of the human-specific, inhibitory antibody 5D3 that recognizes extracellular loops of the transporter. We observe two cholesterol molecules bound in the multidrug-binding pocket that is located in a central, hydrophobic, inward-facing translocation pathway between the transmembrane domains. Combined with functional in vitro analyses, our results suggest a multidrug recognition and transport mechanism of ABCG2, rationalize disease-causing single nucleotide polymorphisms and the allosteric inhibition by the 5D3 antibody, and provide the structural basis of cholesterol recognition by other G-subfamily ABC transporters.

PubMed: 28554189
DOI: 10.1038/nature22345

実験手法

X-RAY DIFFRACTION (1.498 Å)