TY  - JOUR
AU  - Prescher, Martin
AU  - Bonus, Michele
AU  - Stindt, Jan
AU  - Keitel-Anselmino, Verena
AU  - Smits, Sander H. J.
AU  - Gohlke, Holger
AU  - Schmitt, Lutz
TI  - Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4
JO  - Structure
VL  - 29
IS  - 10
SN  - 0969-2126
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - FZJ-2021-02626
SP  - 1144-1155.e5
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34107287
UR  - <Go to ISI:>//WOS:000743716700006
DO  - DOI:10.1016/j.str.2021.05.013
UR  - https://juser.fz-juelich.de/record/893209
ER  -