A cross-species comparison of the apolipoprotein B domain that binds to the LDL receptor.
Apolipoprotein (apo)-B-100 is the ligand that mediates the clearance of low density lipoprotein (LDL) from the circulation by the apoB,E (LDL) receptor pathway. Clearance is mediated by the interaction of a domain enriched in basic amino acid residues on apoB-100 with clusters of acidic residues on the apoB,E (LDL) receptor. A model has been proposed for the LDL receptor binding domain of apoB-100 based on the primary amino acid sequence (Knott, T. J., et al. 1986. Nature. 323: 734-738). Two clusters of basic residues (A: 3147-3157 and B: 3359-3367) are apposed on the surface of the LDL particle by a disulfide bridge between Cys 3167 and 3297. Support for this single domain model has been obtained from the mapping of epitopes for anti-apoB monoclonal antibodies that block the binding of apoB to the LDL receptor. Here we test this model by comparing the nucleotide (from 9623 to 10,442) and amino acid sequence (from 3139 to 3411) of apoB-100 in seven species (human, pig, rabbit, rat, Syrian hamster, mouse, and chicken). Overall, this region is highly conserved. Cluster B maintains a strong net positive charge and is homologous across species in both primary and secondary structure. However, the net positive charge of region A is not conserved across these species, but the region remains strongly hydrophilic. The secondary structure of the region between clusters A and B is preserved, but the disulfide bond is unique to the human sequence. This study suggests that the basic region B is primarily involved in the binding of apoB-100 to the apoB,E (LDL) receptor.
Law
A
A
Division of Molecular Medicine, Clinical Research Centre, Harrow, Middlesex, UK.
Scott
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000032:analysis* / Q000378:metabolism; D001483:Base Sequence; D002645:Chickens; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine
D001055:Apolipoproteins B; D011973:Receptors, LDL