CRYSTAL-STRUCTURE OF HUMAN CHARCOT-LEYDEN CRYSTAL PROTEIN, AN EOSINOPHIL LYSOPHOSPHOLIPASE, IDENTIFIES IT AS A NEW MEMBER OF THE CARBOHYDRATE-BINDING FAMILY OF GALECTINS

Background: The Charcot-Leyden crystal (CLC) protein is a major autocr ystallizing constituent of human eosinophils and basophils, comprising similar to 10% of the total cellular protein in these granulocytes. i dentification of the distinctive hexagonal bipyramidal crystals of CLC protein in body fluids and secretions has long been considered a hall mark of eosinophil-associated allergic inflammation. Although CLC prot ein possesses lysophospholipase activity, its role(s) in eosinophil or basophil function or associated inflammatory responses has remained s peculative. Results: The crystal structure of the CLC protein has been determined at 1.8 Angstrom resolution using X-ray crystallography. Th e overall structural fold of CLC protein is highly similar to that of galectins -1 and -2, members of an animal lectin family formerly class ified as S-type or S-Lac (soluble lactose-binding) lectins. This is th e first structure of an eosinophil protein to be determined and the hi ghest resolution structure so far determined for any member of the gal ectin family. Conclusions: The CLC protein structure possesses a carbo hydrate-recognition domain comprising most, but not ail, of the carboh ydrate-binding residues that are conserved among the galectins. The pr otein exhibits specific (albeit weak) carbohydrate-binding activity fo r simple saccharides including N-acetyl-D-glucosamine and lactose. Des pite CLC protein having no significant sequence or structural similari ties to other lysophospholipases or lipolytic enzymes, a possible lyso phospholipase catalytic triad has also been identified within the CLC structure, making it a unique dual-function polypeptide. These structu ral findings suggest a potential intracellular and/or extracellular ro le(s) for the galectin-associated activities of CLC protein in eosinop hil and basophil function in allergic diseases and inflammation.