Molecular parameters that control the association of low density lipoprotein apo B-100 with chondroitin sulphate.
The association of low density lipoprotein (LDL) with proteoglycans of the arterial intima, in particular chondroitin 6-sulphate proteoglycans, may contribute to LDL accumulation during atherogenesis. We studied the interactions of apolipoprotein B-100 (apo B-100) peptide segments and model peptides with chondroitin 6-sulphate. The ability of these peptides to inhibit complex formation between LDL and chondroitin 6-sulphate was used as a measurement of the interaction. Results from earlier studies suggest that surface located segments of apo B-100 are responsible for the interaction of LDL with heparin and chondroitin sulphate-rich arterial proteoglycans. Therefore 16 hydrophilic apo B-100 peptides were selected for studies and synthesized with a peptide synthesizer. These synthetic peptides were 7 to 26 amino acids long. Four of the peptides inhibited the association of LDL with chondroitin 6-sulphate, namely apo B segments 4230-4254, 3359-3377, 3145-3157 and 2106-2121. The 3359-3377 segment was the most efficient. A common feature between the interacting peptides was an excess of positively charged side chains and based on these results we synthesized nine model peptides that shared sequence characteristics with the interacting apo B-100 peptides. Five of these: RSGRKRSGK, RSSRKRSGK, RGGRKRGGK, RSRSRSRSR and RGRGRGRGR were shown to block the LDL-chondroitin-6-sulphate association, RSRSRSRSR being the most effective. The results suggest that the optimal association of the peptides with chondroitin 6-sulphate is obtained with a minimal chain length of nine amino acids and a minimum of five positive charges and that flexibility in the binding region is important.
Olsson
U
U
Wallenberg Laboratory for Cardiovascular Research, Department of Medicine 1, University of Göteborg, Sweden.
Camejo
G
G
Olofsson
S O
SO
Bondjers
G
G
D000595:Amino Acid Sequence; D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002942:Circular Dichroism; D003198:Computer Simulation; D004563:Electrochemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011487:Protein Conformation
D001055:Apolipoproteins B; D010455:Peptides; D002809:Chondroitin Sulfates