A lectin from the mussel Mytilus galloprovincialis has a highly novel primary structure and induces glycan-mediated cytotoxicity of globotriaosylceramide-expressing lymphoma cells.
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| Abstract |
A novel lectin structure was found for a 17-kDa α-D-galactose-binding lectin (termed "MytiLec") isolated from the Mediterranean mussel, Mytilus galloprovincialis. The complete primary structure of the lectin was determined by Edman degradation and mass spectrometric analysis. MytiLec was found to consist of 149 amino acids with a total molecular mass of 16,812.59 Da by Fourier transform-ion cyclotron resonance mass spectrometry, in good agreement with the calculated value of 16,823.22 Da. MytiLec had an N terminus of acetylthreonine and a primary structure that was highly novel in comparison with those of all known lectins in the structure database. The polypeptide structure consisted of three tandem-repeat domains of ∼50 amino acids each having 45-52% homology with each other. Frontal affinity chromatography technology indicated that MytiLec bound specifically to globotriose (Gb3; Galα1-4Galβ1-4Glc), the epitope of globotriaosylceramide. MytiLec showed a dose-dependent cytotoxic effect on human Burkitt lymphoma Raji cells (which have high surface expression of Gb3) but had no such effect on erythroleukemia K562 cells (which do not express Gb3). The cytotoxic effect of MytiLec was specifically blocked by the co-presence of an α-galactoside. MytiLec treatment of Raji cells caused increased binding of anti-annexin V antibody and incorporation of propidium iodide, which are indicators of cell membrane inversion and perforation. MytiLec is the first reported lectin having a primary structure with the highly novel triple tandem-repeat domain and showing transduction of apoptotic signaling against Burkitt lymphoma cells by interaction with a glycosphingolipid-enriched microdomain containing Gb3.
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| Authors | Yuki Fujii, Naoshi Dohmae, Koji Takio, Sarkar M A Kawsar, Ryo Matsumoto, Imtiaj Hasan, Yasuhiro Koide, Robert A Kanaly, Hidetaro Yasumitsu, Yukiko Ogawa, Shigeki Sugawara, Masahiro Hosono, Kazuo Nitta, Jiharu Hamako, Taei Matsui, Yasuhiro Ozeki |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 53 Pg. 44772-83 (Dec 28 2012) ISSN: 1083-351X [Electronic] United States |
| PMID | 23093409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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