6lf2
From Proteopedia
SeviL bound to asialo-GM1 saccharide
Structural highlights
FunctionLECS1_MYTVI Galbeta1-3GalNAcbeta1-4Galbeta1-4Glc oligosaccharide-binding lectin. Binds strongly to the oligosaccharides of ganglioside GM1b and to a lesser extent its precursor asialo-GM1 (PubMed:31769916, PubMed:33328520). Binds weakly to asialo-GM2 oligosaccharide and to the glycan moiety of globo-series stage-specific embryonal antigen 4 (SSEA-4) hexaose (PubMed:31769916). Binds galactose, N-acetylgalactose and lactose. Does not bind GM1 (PubMed:33328520). Does not bind to Gal-beta1,3-GalNAc (Thomsen-Friedenreich antigen), the oligosaccharide of GM1a ganglioside or SSEA-4 tetraose. Does not bind to N-glycans, O-glycans or glycosaminoglycans of glycoproteins. Does not bind Lewis glycans, derivatives of lactose or N-acetyllactosamine or blood group (ABH-type) oligosaccharides (PubMed:31769916). Does not bind glucose (PubMed:33328520). Has hemagglutination activity towards rabbit erythrocytes (PubMed:31769916, PubMed:33328520). Displays cytotoxic effects against various cultured cell lines including human breast (MCF-7), cervical (HeLa) and colon cancer (Caco2) cell lines, as well as dog kidney (MDCK) cell line that express asialo-GM1 oligosaccharide at their cell surface. Shows dose- and time-dependent activation of MKK3/6, ERK1/2 and p38 MAPK, as well as caspase-3/9 in HeLa cervical cancer cells. No cytotoxic effect on BT474 human breast cancer cell line. May be involved in recognition of glycans found on parasitic or symbiotic microorganisms (PubMed:31769916).[1] [2] Publication Abstract from PubMedSeviL is a recently isolated lectin found to bind to the linear saccharides of the ganglioside GM1b (Neu5Ac[Formula: see text](2-3)Gal[Formula: see text](1-3)GalNAc[Formula: see text](1-4)Gal[Formula: see text](1-4)Glc) and its precursor, asialo-GM1 (Gal[Formula: see text](1-3)GalNAc[Formula: see text](1-4)Gal[Formula: see text](1-4)Glc). The crystal structures of recombinant SeviL have been determined in the presence and absence of ligand. The protein belongs to the [Formula: see text]-trefoil family, but shows only weak sequence similarity to known structures. SeviL forms a dimer in solution, with one binding site per subunit, close to the subunit interface. Molecular details of glycan recognition by SeviL in solution were analysed by ligand- and protein-based NMR techniques as well as ligand binding assays. SeviL shows no interaction with GM1 due to steric hindrance with the sialic acid branch that is absent from GM1b. This unusual specificity makes SeviL of great interest for the detection and control of certain cancer cells, and cells of the immune system, that display asialo-GM1. The structure of SeviL, a GM1b/asialo-GM1 binding R-type lectin from the mussel Mytilisepta virgata.,Kamata K, Mizutani K, Takahashi K, Marchetti R, Silipo A, Addy C, Park SY, Fujii Y, Fujita H, Konuma T, Ikegami T, Ozeki Y, Tame JRH Sci Rep. 2020 Dec 16;10(1):22102. doi: 10.1038/s41598-020-78926-7. PMID:33328520[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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