Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor.

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 separat

SUBMITTER: Barbieri A 

PROVIDER: S-EPMC8703531 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature