title: Eosinophil-granule major basic protein, a C-type lectin, binds heparin.
abstract: The eosinophil major basic protein (EMBP), a constituent of the eosinophil secondary granule, is implicated in cytotoxicity and mediation of allergic disorders such as asthma. It is a member of the C-type lectin family, but lacks a Ca(2+)- and carbohydrate-binding site as seen in other members of this family. Here, we report the crystal structure of EMBP in complex with a heparin disaccharide and in the absence of Ca(2+), the first such report of any C-lectin with this sugar. We also provide direct evidence of binding of EMBP to heparin and heparin disaccharide by surface plasmon resonance. We propose that the sugars recognized by EMBP are likely to be proteoglycans such as heparin, leading to new interpretations for EMBP function.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
authors.forename: G Jawahar
authors.initials: GJ
authors.lastname: Swaminathan
authors.forename: David G
authors.initials: DG
authors.lastname: Myszka
authors.forename: Phinikoula S
authors.initials: PS
authors.lastname: Katsamba
authors.forename: Lyo E
authors.initials: LE
authors.lastname: Ohnuki
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D002236:Carbohydrate Conformation; D002413:Cations, Divalent; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry; D047093:Eosinophil Major Basic Protein / Q000737:chemistry*; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D037102:Lectins / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000925:Anticoagulants; D002413:Cations, Divalent; D004187:Disaccharides; D037102:Lectins; C059525:cerebellar soluble lectin; C464536:heparin disaccharide; D006493:Heparin; D047093:Eosinophil Major Basic Protein; D002118:Calcium