%0 Journal Article
%A Prescher, Martin
%A Bonus, Michele
%A Stindt, Jan
%A Keitel-Anselmino, Verena
%A Smits, Sander H. J.
%A Gohlke, Holger
%A Schmitt, Lutz
%T Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4
%J Structure
%V 29
%N 10
%@ 0969-2126
%C Cambridge, Mass.
%I Cell Press
%M FZJ-2021-02626
%P 1144-1155.e5
%D 2021
%X ABCB4 is described as an ATP-binding cassette (ABC) transporter that primarily transports lipids of the phosphatidylcholine (PC) family but is also capable of translocating a subset of typical multidrug-resistance-associated drugs. The high degree of amino acid identity of 76% for ABCB4 and ABCB1, which is a prototype multidrug-resistance-mediating protein, results in ABCB4's second subset of substrates, which overlap with ABCB1's substrates. This often leads to incomplete annotations of ABCB4, in which it was described as exclusively PC-lipid specific. When the hydrophilic amino acids from ABCB4 are changed to the analogous but hydrophobic ones from ABCB1, the stimulation of ATPase activity by 1,2-dioleoyl-sn-glycero-3-phosphocholine, as a prime example of PC lipids, is strongly diminished, whereas the modulation capability of ABCB1 substrates remains unchanged. This indicates two distinct and autonomous substrate binding sites in ABCB4.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 34107287
%U <Go to ISI:>//WOS:000743716700006
%R 10.1016/j.str.2021.05.013
%U https://juser.fz-juelich.de/record/893209