Chimeric structural stabilities in the coiled-coil structure of the NECK domain in human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1).
LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1) is the major oxidized LDL (OxLDL) receptor on endothelial cells. The extracellular part of LOX-1 comprises an 82-residue stalk region (NECK) and a C-type lectin-like ligand-binding domain (CTLD). The NECK displays sequence similarity to the coiled-coil region of myosin, having been suggested it adopts a rod-like structure. In this article, we report the structural analyses of human LOX-1 NECK using a variety of approaches including limited proteolysis, chemical cross-linking, circular dichroism (CD) and NMR. Our analysis reveals a unique structural feature of the LOX-1 NECK. Despite significant sequence similarity with the myosin coiled-coil, LOX-1 NECK does not form a uniform rod-like structure. Although not random, one-third of the N-terminal NECK is less structured than the remainder of the protein and is highly sensitive to cleavage by a variety of proteases. The coiled-coil structure is localized at the C-terminal part of the NECK, but is in dynamic equilibrium among multiple conformational states on a mus-ms time scale. This chimeric structural property of the NECK region may enable clustered LOX-1 on the cell surface to recognize OxLDL.
Ishigaki
Tomoko
T
Department of Structural Biology, Biomolecular Engineering Research Institute (BERI), 6-2-3, Furuedai, Suita, Osaka, Japan.
Ohki
Izuru
I
Utsunomiya-Tate
Naoko
N
Tate
Shin-Icih
SI
D000595:Amino Acid Sequence; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D002942:Circular Dichroism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010100:Oxygen; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D051127:Scavenger Receptors, Class E / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D008024:Ligands; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; D051127:Scavenger Receptors, Class E; D010100:Oxygen