title: The histidine interruption of an alpha-helical coiled coil allosterically mediates a pH-dependent ligand dissociation from macrophage scavenger receptors.
abstract: Macrophage scavenger receptors uptake modified low density lipoproteins (LDLs) through receptor-mediated endocytosis. In the alpha-helical coiled coil domain, 2 histidines (His168 and His260) disrupt leucine or isoleucine heptad repeats. Substitution of His168 or/and His260 to leucine had no effect on AcLDL binding activities. However, the His260-replaced receptors had their ligand degradation activities diminished. Cell surface ligand release experiments under acidic pH clarified that His260 mutants lost their ligand dissociation activities at 37 degrees C. Furthermore, immunoelectron microscopic experiments using anti-scavenger receptor antibody showed that the His260 replaced receptors were not able to release gold-labeled AcLDL in endosomes. Here we propose an allosterical ligand dissociation mechanism by His260 in macrophage scavenger receptors.
authors.affiliation: Faculty of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Doi
authors.forename: M
authors.initials: M
authors.lastname: Kurasawa
authors.forename: K
authors.initials: K
authors.lastname: Higashino
authors.forename: T
authors.initials: T
authors.lastname: Imanishi
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Matsumoto
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004705:Endocytosis; D017979:Gold Colloid; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D014162:Transfection
chemical_list: D017979:Gold Colloid; D008024:Ligands; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C032629:acetyl-LDL; D006639:Histidine