Eosinophil-granule major basic protein, a C-type lectin, binds heparin.
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.
Swaminathan
G Jawahar
GJ
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
Myszka
David G
DG
Katsamba
Phinikoula S
PS
Ohnuki
Lyo E
LE
Gleich
Gerald J
GJ
Acharya
K Ravi
KR
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
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