7OTI

Structure of ABCB1/P-glycoprotein in apo state

7OTI の概要

• エントリーDOI: 10.2210/pdb7oti/pdb
• 関連するPDBエントリー: 7OTG
• EMDBエントリー: 13059 13060
• 分子名称: Multidrug resistance protein 1A (1 entity in total)
• 機能のキーワード: abcb1, abc transporters, membrane proteins, ivacaftor, mdr1, multidrug resistance, cryo-em, membrane protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 141877.88

構造登録者

Ford, R.C.,Barbieri, A.,Thonghin, N.,Shafi, T.,Prince, S.M.,Collins, R.F. (登録日: 2021-06-10, 公開日: 2021-12-08, 最終更新日: 2024-07-17)

主引用文献

Barbieri, A.,Thonghin, N.,Shafi, T.,Prince, S.M.,Collins, R.F.,Ford, R.C.
Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor.
Membranes (Basel), 11:-, 2021

PubMed Abstract: ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of the protein within the membrane is an intrinsic part of its mechanism of action, but this has made structural studies challenging. Here, we have studied different conformations of P-glycoprotein simultaneously in the presence of ivacaftor, a known competitive inhibitor. In order to conduct this, we used high contrast cryo-electron microscopy imaging with a Volta phase plate. We associate the presence of ivacaftor with the appearance of an additional density in one of the conformational states detected. The additional density is in the central aqueous cavity and is associated with a wider separation of the two halves of the transporter in the inward-facing state. Conformational changes to the nucleotide-binding domains are also observed and may help to explain the stimulation of ATPase activity that occurs when transported substrate is bound in many ATP binding cassette transporters.

PubMed: 34940424
DOI: 10.3390/membranes11120923

実験手法

ELECTRON MICROSCOPY (4.2 Å)