cDNA cloning and structural characterization of a lectin from the mussel Crenomytilus grayanus with a unique amino acid sequence and antibacterial activity

Kovalchuk, Svetlana N.; Chikalovets, I. V.; Chernikov, Oleg V.; Molchanova, V. I.; Li, Wei; Rasskazov, V. A.; Lukyanov, Pavel

doi:10.1016/j.fsi.2013.07.011

Cited by 43 publications

(45 citation statements)

References 15 publications

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“…Overall, about 20 different genes encoding proteins with a ricin domain are present in the C. gigas genome: most of them pertain to the well-known class of a-N-acetylgalactosaminyltransferases, enzymes which are involved in the biosynthesis of Mucin-type O-glycans. A novel lectin named MytiLec, with globotriose-dependent cytotoxicity, has been recently identified in M. galloprovincialis [65], and later a very similar lectin with antibacterial activity was identified in Crenomytilus grayanus [66]. These lectins share a structural motif with three very similar tandem repeats of about 50 amino acids, recognizable as a ricin-type beta trefoil domain.…”

Section: Extracellular Prrsmentioning

confidence: 99%

An updated molecular basis for mussel immunity

Gerdol

Venier

2015

Fish & Shellfish Immunology

134

163

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Non-self recognition with the consequent tolerance or immune reaction is a crucial process to succeed as living organisms. At the same time the interactions between host species and their microbiome, including potential pathogens and parasites, significantly contribute to animal life diversity. Marine filter-feeding bivalves, mussels in particular, can survive also in heavily anthropized coastal waters despite being constantly surrounded by microorganisms. Based on the first outline of the Mytilus galloprovincialis immunome dated 2011, the continuously growing transcript data and the recent release of a draft mussel genome, we explored the available sequence data and scientific literature to reinforce our knowledge on the main gene-encoded elements of the mussel immune responses, from the pathogen recognition to its clearance. We carefully investigated molecules specialized in the sensing and targeting of potential aggressors, expected to show greater molecular diversification, and outlined, whenever relevant, the interconnected cascades of the intracellular signal transduction. Aiming to explore the diversity of extracellular, membrane-bound and intracellular pattern recognition receptors in mussel, we updated a highly complex immune system, comprising molecules which are described here in detail for the first time (e.g. NOD-like receptors) or which had only been partially characterized in bivalves (e.g. RIG-like receptors). Overall, our comparative sequence analysis supported the identification of over 70 novel full-length immunity-related transcripts in M. galloprovincialis. Nevertheless, the multiplicity of gene functions relevant to immunity, the involvement of part of them in other vital processes, and also the lack of a refined mussel genome make this work still not-exhaustive and support the development of more specific studies.

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Section: Extracellular Prrsmentioning

confidence: 99%

An updated molecular basis for mussel immunity

Gerdol

Venier

2015

Fish & Shellfish Immunology

134

163

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“…The polypeptide chain has three well-conserved repeats of a roughly 50-residue sequence, and adopts a β -trefoil fold. Together with two other sea-mussel proteins, Crenomytilus grayanus lectin (CGL) 2 and Mytilus trossulus lectin (MTL) 3 , MytiLec forms a small subfamily of closely related lectins with no sequence similarity to other proteins. They show bacteriostatic properties, and appear to play a role in innate immunity, alongside other shellfish lectins 4, 5 .…”

Section: Introductionmentioning

confidence: 99%

Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity

Terada

Voet

Noguchi

et al. 2017

Sci Rep

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Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt’s lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called “Mitsuba”, is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bind α-D-galactose. The three subdomains of MytiLec-1 each carry one galactose binding site, and the 149-residue protein forms a tight dimer in solution. Mitsuba (meaning “three-leaf” in Japanese) was created by symmetry constraining the structure of a MytiLec-1 subunit, resulting in a 150-residue sequence that contains three identical tandem repeats. Mitsuba-1 was expressed and crystallised to confirm the X-ray structure matches the predicted model. Mitsuba-1 recognises cancer cells that express globotriose (Galα(1,4)Galβ(1,4)Glc) on the surface, but the cytotoxicity is abolished.

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“…It has three broadly similar repeats of a sequence about 45 residues long, highly conserved at certain positions, and a single tryptophan residue near the start of the second repeat. MytiLec has no significant sequence similarity to any known protein, except Crenomytilus grayanus lectin (CGL)2 and Mytilus trossulus lectin (MTL)3, from two different species of sea mussel, which both share 88% sequence identity with MytiLec. The natural function of these proteins appears to be anti-bacterial or anti-fungal, and they show bacteriostatic properties.…”

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confidence: 99%

Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types

Terada

Kawai

Noguchi

et al. 2016

Sci Rep

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MytiLec is a lectin, isolated from bivalves, with cytotoxic activity against cancer cell lines that express globotriaosyl ceramide, Galα(1,4)Galβ(1,4)Glcα1-Cer, on the cell surface. Functional analysis shows that the protein binds to the disaccharide melibiose, Galα(1,6)Glc, and the trisaccharide globotriose, Galα(1,4)Galβ(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.

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cDNA cloning and structural characterization of a lectin from the mussel Crenomytilus grayanus with a unique amino acid sequence and antibacterial activity

Cited by 43 publications

References 15 publications

An updated molecular basis for mussel immunity

An updated molecular basis for mussel immunity

Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity

Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types

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