The article by Cardin and Weintraub explores the molecular interactions between proteins and glycosaminoglycans (GAGs), particularly heparin. They identified 49 potential heparin-binding sites in 21 proteins based on the sequence organization of basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to develop two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for GAG recognition were determined as (-X-B-X-B-X-X-) and (-X-B-B-X-B-X-X-) where B represents a basic residue and X represents a hydrophobic residue. Predictions were made for heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs exhibit prominent amphipathic periodicities with both α-helical and β-strand conformations. The heparin-binding domain of vitronectin was modeled, forming a hydrophilic pocket that wraps around and folds over a heparin octasaccharide, yielding a complementary structure. These consensus sequence elements may serve as potential nucleation sites for the recognition of polyanions in proteins and could provide a useful guide for identifying heparin-binding regions in other proteins. The relevance of protein-GAG interactions in atherosclerosis is also discussed.The article by Cardin and Weintraub explores the molecular interactions between proteins and glycosaminoglycans (GAGs), particularly heparin. They identified 49 potential heparin-binding sites in 21 proteins based on the sequence organization of basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to develop two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for GAG recognition were determined as (-X-B-X-B-X-X-) and (-X-B-B-X-B-X-X-) where B represents a basic residue and X represents a hydrophobic residue. Predictions were made for heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs exhibit prominent amphipathic periodicities with both α-helical and β-strand conformations. The heparin-binding domain of vitronectin was modeled, forming a hydrophilic pocket that wraps around and folds over a heparin octasaccharide, yielding a complementary structure. These consensus sequence elements may serve as potential nucleation sites for the recognition of polyanions in proteins and could provide a useful guide for identifying heparin-binding regions in other proteins. The relevance of protein-GAG interactions in atherosclerosis is also discussed.