title: Position 834 in TM6 plays an important role in cholesterol and phosphatidylcholine transport by ABCA1.
abstract: ATP-binding cassette protein A1 (ABCA1) plays a key role in eliminating excess cholesterol from peripheral cells by generating nascent high-density lipoprotein (HDL). However, it remains unclear whether both phospholipids and cholesterol are directly loaded onto apolipoprotein A-I (apoA-I) by ABCA1. To identify the amino acid residues of ABCA1 involved in substrate recognition and transport, we applied arginine scan mutagenesis to residues L821-E843 of human ABCA1 and predicted the environment to which each residue is exposed. The relative surface expression of each mutant suggested that residues L821-E843 pass through the plasma membrane as TM6, and the four residues (S826, F830, L834, and V837) of TM6 are exposed to the hydrophilic internal cavity of ABCA1. Furthermore, we showed that L834 is critical for the function of ABCA1.
authors.affiliation: a Laboratory of Cellular Biochemistry, Division of Applied Life Sciences , Kyoto University Graduate School of Agriculture , Kyoto , Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Itoh
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kimura
authors.forename: Michinori
authors.initials: M
authors.lastname: Matsuo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D010713:Phosphatidylcholines / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D010713:Phosphatidylcholines; D001120:Arginine; D002784:Cholesterol
keywords: ABC protein; ABCA1; cholesterol; high-density lipoprotein (HDL); transporter