title: The aggregation of basic polypeptide residues bound to heparin.
abstract: The molecular basis for heparin interactions with proteins has been explored with L-lysine copolymer : heparin complexes, measuring the conformational change and charge neutralization which accompany the complexation, using optical methods. Previous studies had shown that the basic homopolypeptides (poly-L-lysine, poly-L-arginine) assume alpha-helical conformation upon interaction with numerous glycosaminoglycans (including heparin). Thus, the unique specificity for heparin in the anticoagulation system (which involves two or more lysine residues on the antithrombin molecule) is not paralleled by the findings with the basic homopolymers. Results with mixed polypeptides, poly(lysine : tyrosine, 1 : 1) and poly(lysine : phenylalanine, 1.4 : 1), show that these protein models assume different conformational forms upon complexation with heparin, the former shows a poly-L-lysine-like beta-structure circular dichroism spectrum and the latter an alpha-helical structure. The change in circular dichroism spectra increases with the addition of heparin until the ratio of positive to negative charge is about one. Dye-binding studies of the two copolymer systems reveal that the charged groups of both reactants are largely blocked in the polypeptide complexes at a calculated charge ratio equal to one. The data indicate that heparin interaction with the cationic polypeptides causes them to assume either the alpha-helical or beta-structure depending upon the nature of the neighboring uncharged amino acid and its proclivity for alpha-helix or beta-structure.
mesh_terms: D055598:Chemical Phenomena; D002621:Chemistry; D002942:Circular Dichroism; D006493:Heparin / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010649:Phenylalanine; D011107:Polylysine; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014443:Tyrosine
chemical_list: D010455:Peptides; D011107:Polylysine; D014443:Tyrosine; D010649:Phenylalanine; D006493:Heparin