Heparin-binding domains in vascular biology.
Heparin is a major anticoagulant with activity mediated primarily through its interaction with antithrombin (AT). Heparan sulfate (HS), structurally related to heparin, binds a wide range of proteins of different functionality, taking part in various physiological and pathological processes. The heparin-AT complex, the most well understood facet of anticoagulation, serves as a prototypical example of the important role of heparin/HS in vascular biology. Extensive studies have identified common structural features in heparin/HS-binding sites of proteins. These include the elucidation of consensus sequences in proteins, patterns of clusters of basic and nonbasic residues, and common spatial arrangements of basic amino acids in the heparin-binding sites. Although these studies have provided valuable information, heparin/HS-binding proteins differ widely in structure. The prediction of heparin/HS-binding proteins from sequence information is not currently possible, and elucidation of protein-binding sites requires the individual study of each glycosaminoglycan-protein complex. Thus, x-ray crystallography and site-directed mutagenesis experiments are among the most powerful tools, providing accurate structural information, facilitating the characterization of heparin-protein complexes. Heparin and structurally related heparan sulfate bind a large number of proteins, taking part in a wide range of biological processes, particularly ones involved in vascular biology. Heparin-binding domains share certain common structural features, but there is no absolute dependency on specific sequences or protein folds.
Muñoz
Eva M
EM
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Linhardt
Robert J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D000991:Antithrombins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002240:Carbohydrate Sequence; D002317:Cardiovascular Agents / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism*; D016384:Consensus Sequence; D015195:Drug Design; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D000991:Antithrombins; D001798:Blood Proteins; D002317:Cardiovascular Agents; D006493:Heparin