Lipid-induced recognition of a conformational determinant (residues 65 to 83) in myelin basic protein.
The precipitation by antibodies to intact myelin basic protein (BP) and to synthetic peptides containing a sequence based on the region 65 to 83 of bovine BP, S82, S81, S79, and S24, of intact BP in solution or bound to lipid vesicles was compared, using 125I-BP or 14C-DPPC-labeled lipid-BP vesicles. The antipeptide antibodies were shown earlier to recognize conformational determinants which are not expressed in the intact protein in solution. Several anti-BP antibodies precipitated more of the BP free in solution than when bound to lipid vesicles, suggesting that some of the determinants recognized by these antibodies were either sequestered in the bilayer or were altered in conformation. In contrast, one anti-peptide antisera, which had a high titer for the conformational determinant in two of these peptides, S82 and S81, precipitated the protein to a significant degree when it was bound to PG vesicles, even though it did not react with the intact protein in solution. These results indicated that PG was able to confer on the protein the unique peptide conformation recognized by this antibody. PS was less effective, and other lipids were ineffective at conferring this conformation on the protein, supporting earlier results which showed that the conformation of the protein is influenced by the lipid composition of its environment. None of the other anti-peptide antibodies studied bound to the protein either in solution or in lipid vesicles. These results indicate that the lipid environment can sequester or alter the conformation of some antigenic determinants, preventing recognition by some anti-BP antibodies, and can expose or generate other conformational determinants, allowing recognition by an anti-peptide antiserum.
Boggs
J M
JM
Hashim
G A
GA
Day
E D
ED
Moscarello
M A
MA
D000818:Animals; D000906:Antibodies / Q000502:physiology*; D001666:Binding Sites, Antibody; D002417:Cattle; D000939:Epitopes / Q000276:immunology; D006168:Guinea Pigs; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011233:Precipitin Tests; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D000939:Epitopes; D008055:Lipids; D004676:Myelin Basic Protein; D010455:Peptides