Ability of the LDL receptor from several animal species to recognize the human apo B binding domain: studies with LDL from familial defective apo B-100.
To verify whether the LDL receptors from different animal species recognize the binding domain of human apo B-100 we studied the interaction of LDL from control and familial binding defective apo B-100 (FDB) with cultured cells. Human, monkey, bovine, guinea pig and rabbit LDL receptors distinguish between normal and binding defective LDL with a displacement ratio (defective/normal) of 3.3, 2.6, 3.4, 3.1 and 2.0, respectively. Guinea pig and rabbit receptors, however, showed affinities 2-3-fold lower than the human receptor. Hamster, rat and mouse cells failed to differentiate between normal and FDB LDL with a ratio of 1.2, 0.8, and 1.4; the apparent affinities were 4-8 times lower than that of the human receptor. The data from the latter species suggest that the LDL receptor recognizes an area of human apo B different from the human receptor binding domain. The ability of antibody Mb47 to inhibit the binding of human LDL to human, rabbit and guinea pig but not to mouse cells further stresses this concept. Moreover, in 17 alpha-ethinyl estradiol-treated rats the rate of disappearance from plasma of FDB and control 125I-labelled LDL was identical, thus confirming the in vitro observations. These data suggest that the binding domain of the LDL receptor is functionally conserved in man, monkey, cow, rabbit and guinea pig, but is quite distinct in rat, mouse and hamster.
Corsini
A
A
Institute of Pharmacological Sciences, University of Milano, Italy.
Mazzotti
M
M
Villa
A
A
Maggi
F M
FM
Bernini
F
F
Romano
L
L
Romano
C
C
Fumagalli
R
R
Catapano
A L
AL
D000818:Animals; D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000378:metabolism*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011973:Receptors, LDL