Is apolipoprotein D a mammalian bilin-binding protein?
Human apolipoprotein D (APO-D) is a serum glycoprotein that has no sequence similarity with other apolipoproteins but rather belongs to the alpha 2-microglobulin superfamily whose other members transport small hydrophobic ligands in a wide variety of biological contexts. To investigate the ligand specificity of APO-D, we analyzed its relationship with the other members of this superfamily and constructed a detailed molecular model using the atomic coordinates of its most closely related homolog--insecticyanin from the tobacco hornworm, Manduca sexta. We studied the geometry of the binding pocket of APO-D and the topology of characteristic patches of both hydrophobic and polar side chains that also occur in crystal structures of insecticyanin and bilin-binding protein from the butterfly Pieris brassicae. From the data obtained we hypothesize that heme-related compounds may be more favorable ligands for APO-D than either cholesterol or cholesteryl ester. Preliminary experiments showed that purified human APO-D binds bilirubin in an approximately one-to-one molar ratio. These results suggest a new biological role for APO-D that is more congruent with its tissue distribution and evolutionary history.
Peitsch
M C
MC
Laboratory of Mathematical Biology, National Cancer Institute, Frederick, MD 21701.
Boguski
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D053399:Apolipoproteins D; D001665:Binding Sites; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007301:Insect Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins; D007447:Invertebrate Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D007301:Insect Hormones; D019476:Insect Proteins; D007447:Invertebrate Hormones; D008024:Ligands; C053849:bilin-binding protein, insect; C043409:insecticyanin protein, insect