caa a22 4500 463208358 CHVBK 20180405153132.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10863-007-9109-7 doi (NATIONALLICENCE)springer-10.1007/s10863-007-9109-7 Cholesterol fill-in model: mechanism for substrate recognition by ABC proteins [Elektronische Daten] [Yasuhisa Kimura, Atsushi Kodan, Michinori Matsuo, Kazumitsu Ueda] Many of the 48 or 49 human ABC proteins are involved in lipid homeostasis and in defence against hydrophobic substances in food and the environment. Defects in their functions cause various diseases, suggesting that they play very important roles in human health; however, the mechanism of how they handle enormous numbers of hydrophobic compounds with various structures and molecular weights, or phospholipids and cholesterol, major components of cellular membranes, is not known. We compared the functions of drug-transporting and lipid-transporting ABC proteins, and found that (1) ABC proteins, either lipid or drug transporters, have a similar substrate binding site which recognizes PL and cholesterol, or drugs and cholesterol; (2) Cholesterol in membranes binds to various ABC proteins together with PL or drugs, and plays an important role in substrate recognition, especially by ABCB1/MDR1, where cholesterol fills the empty space in the substrate binding site when small drugs bind to it. ABC proteins exert very flexible substrate recognition, i.e., one-to-many interaction rather than the conventional rigid one-to-one interaction. We propose calling the mechanism the "cholesterol fill-in model”. Springer Science+Business Media, LLC, 2007 ABC proteins nationallicence Lipid transporter nationallicence Drug transporter nationallicence Cholesterol nationallicence MDR1 nationallicence ABCA1 nationallicence Kimura Yasuhisa Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut Kodan Atsushi Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut Matsuo Michinori Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut Ueda Kazumitsu Institute for Integrated Cell-Material Sciences and Laboratory of Cellular Biochemistry,Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 447-452 0145-479X 39:5-6<447 2007 39 10863 https://doi.org/10.1007/s10863-007-9109-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10863-007-9109-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kimura Yasuhisa Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut NATIONALLICENCE 700 1- Kodan Atsushi Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut NATIONALLICENCE 700 1- Matsuo Michinori Laboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut NATIONALLICENCE 700 1- Ueda Kazumitsu Institute for Integrated Cell-Material Sciences and Laboratory of Cellular Biochemistry,Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 606-8502, Kyoto, Japan aut NATIONALLICENCE 773 0- Journal of Bioenergetics and Biomembranes Springer US; http://www.springer-ny.com 39/5-6(2007-12-01), 447-452 0145-479X 39:5-6<447 2007 39 10863 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer