cDNA cloning and expression of oxysterol-binding protein, an oligomer with a potential leucine zipper.
Feedback repression of the genes encoding the low density lipoprotein receptor and several enzymes of the cholesterol biosynthetic pathway is mediated by 25-hydroxycholesterol and other oxysterols. In this study, we have cloned a rabbit cDNA encoding an oxysterol-binding protein that may play a role in this regulation. The predicted amino acid sequence revealed a protein of 809 amino acids with two distinctive features: 1) a glycine- and alanine-rich region (63% of 80 residues) at the NH2 terminus, and 2) a 35-residue leucine zipper motif that may mediate the previously observed oligomerization of the protein. When transfected into simian COS cells, the rabbit cDNA produced a protein that exhibited the same affinity and specificity for sterols as the previously purified hamster liver protein. Immunoblotting analysis showed that the rabbit cDNA encodes both the 96- and 101-kilodalton forms of the oxysterol-binding protein that were previously observed. The availability of an expressible cDNA for the oxysterol-binding protein should help elucidate its role in sterol metabolism.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
P A
PA
Dawson
N D
ND
Ridgway
C A
CA
Slaughter
M S
MS
Brown
J L
JL
Goldstein
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics*; D005784:Gene Amplification; D005796:Genes; D005822:Genetic Vectors; D007700:Kinetics; D007930:Leucine; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008647:Mesocricetus; D008969:Molecular Sequence Data; D011817:Rabbits; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D000098825:Oxysterol Binding Proteins
D046911:Macromolecular Substances; D011987:Receptors, Steroid; D000098825:Oxysterol Binding Proteins; D004247:DNA; D007930:Leucine