Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors.
Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including modified low density lipoproteins (LDL). Truncated bovine receptors lacking residues 330-342, which include the conserved lysine cluster of a collagen-like domain, were unable to degrade modified LDL in spite of their expression on the cell surface. Substitution of lysine 337 into alanine abolished the acetyl-LDL degradation and binding at 37 degrees C, but did not abolish the 4 degrees C binding. In contrast, substitution of more than 2 lysines in this region are needed to abolish the oxidized LDL degradation and 37 degrees C binding. Based on computational modeling of this domain, we propose that a "charged collagen" structure containing a lysine cluster forms a positively charged groove which specifically interacts with negatively charged ligands.
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
T
T
Doi
K
K
Higashino
Y
Y
Kurihara
Y
Y
Wada
T
T
Miyazaki
H
H
Nakamura
S
S
Uesugi
T
T
Imanishi
Y
Y
Kawabe
H
H
Itakura
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D003062:Codon; D003094:Collagen / Q000737:chemistry*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008168:Lung / Q000737:chemistry; D008239:Lysine / Q000235:genetics; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A
D003062:Codon; D006023:Glycoproteins; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D003094:Collagen; D004247:DNA; D008239:Lysine