Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL.
Lectin-like, oxidized low-density lipoprotein (LDL) receptor 1, LOX-1, is the major receptor for oxidized LDL (OxLDL) in endothelial cells. We have determined the crystal structure of the ligand binding domain of LOX-1, with a short stalk region connecting the domain to the membrane-spanning region, as a homodimer linked by an interchain disulfide bond. In vivo assays with LOX-1 mutants revealed that the "basic spine," consisting of linearly aligned arginine residues spanning over the dimer surface, is responsible for ligand binding. Single amino acid substitution in the dimer interface caused a severe reduction in LOX-1 binding activity, suggesting that the correct dimer arrangement is crucial for binding to OxLDL. Based on the LDL model structure, possible binding modes of LOX-1 to OxLDL are proposed.
Ohki
Izuru
I
Department of Structural Biology, Biomolecular Engineering Research Institute 6-2-3, Furuedai, Suita, Osaka, 565-0874, Japan.
Ishigaki
Tomoko
T
Oyama
Takuji
T
Matsunaga
Shigeru
S
Xie
Qiuhong
Q
Ohnishi-Kameyama
Mayumi
M
Murata
Takashi
T
Tsuchiya
Daisuke
D
Machida
Sachiko
S
Morikawa
Kousuke
K
Tate
Shin-ichi
S
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D017124:Conserved Sequence; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D051127:Scavenger Receptors, Class E; D017386:Sequence Homology, Amino Acid
D004220:Disulfides; D008024:Ligands; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D001120:Arginine; D003545:Cysteine