Open AccessCrystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types
Author(s) -
Daiki Terada,
Fumihiro Kawai,
Hideyuki Noguchi,
Satoru Unzai,
Imtiaj Hasan,
Yuki Fujii,
Sam-Yong Park,
Yasuhiro Ozeki,
J.R.H. Tame
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28344
Subject(s) - lectin , raji cell , c type lectin , biochemistry , cytotoxic t cell , cytotoxicity , chemistry , biology , microbiology and biotechnology , cell , in vitro
MytiLec is a lectin, isolated from bivalves, with cytotoxic activity against cancer cell lines that express globotriaosyl ceramide, Gal α (1,4)Gal β (1,4)Glc α 1-Cer, on the cell surface. Functional analysis shows that the protein binds to the disaccharide melibiose, Gal α (1,6)Glc, and the trisaccharide globotriose, Gal α (1,4)Gal β (1,4)Glc. Recombinant MytiLec expressed in bacteria showed the same haemagglutinating and cytotoxic activity against Burkitt’s lymphoma (Raji) cells as the native form. The crystal structure has been determined to atomic resolution, in the presence and absence of ligands, showing the protein to be a member of the β -trefoil family, but with a mode of ligand binding unique to a small group of related trefoil lectins. Each of the three pseudo-equivalent binding sites within the monomer shows ligand binding, and the protein forms a tight dimer in solution. An engineered monomer mutant lost all cytotoxic activity against Raji cells, but retained some haemagglutination activity, showing that the quaternary structure of the protein is important for its cellular effects.