Regional ligand domain is involved in scavenger receptor-mediated recognition of maleyl-albumin by rat sinusoidal liver cells.
Scavenger receptor-mediated endocytosis of maleyl-albumin was studied with rat sinusoidal liver cells. Upon maleylation of greater than 28 mol lysine residues per protein, bovine serum albumin became an active ligand. Further modification of up to 37 mol lysine residues per protein resulted in a sharp increase in the ligand activity, reaching a maximum level thereafter. Removal of maleyl moieties from maleyl-albumin (demaleylation) from 53 mol to 14 mol lysine residues per protein did not affect the ligand activity. However, further demaleylation to less than 5 mol lysine residues per protein led to complete loss of the ligand activity. Thus, the covalently incorporated maleyl moieties are needed for the ligand activity. The ligand activity was also generated when two peptides (Frag N and Frag C) from cyanogen bromide-cleaved albumin were maleylated, indicating that the formation of an active ligand would not require a whole albumin molecule. Maleyl Frag C was further separated into three peptides; maleyl Frag C-1 (261 amino acid residues), maleyl Frag C-2 (102 residues) and maleyl Frag C-3 (36 residues). The cellular binding and endocytic degradation of maleyl-albumin or acetylated low density lipoprotein were effectively competed for by maleyl Frag C-1 and maleyl Frag C-2 but not by maleyl Frag C-3. Thus, regional domains might be involved in the ligand recognition by the scavenger receptor.
Horiuchi
S
S
Department of Biochemistry, Kumamoto University Medical School, Japan.
Takata
K
K
Araki
N
N
Morino
Y
Y
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D004705:Endocytosis; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine / Q000378:metabolism*
D000418:Albumins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C049877:maleylalbumin; D012710:Serum Albumin, Bovine