3nbe
Clitocybe nebularis ricin B-like lectin (CNL) in complex with N,N'-diacetyllactosediamineClitocybe nebularis ricin B-like lectin (CNL) in complex with N,N'-diacetyllactosediamine
Structural highlights
FunctionCNL_CLINE Lectin specific for terminal, non-reducing N-acetylgalactosamine (Gal-NAc)-containing carbohydrates including N,N'-diacetyllactosediamine/LDN (GalNAcbeta1-4GlcNAc, LacdiNAc). Specific also for carbohydrates containing N-acetylglucosamine (-GlcNAc) or N-acetyllactosamine (-Galbeta1-4GlcNAc) at the reducing end. Agglutinates human blood group A, AB, B and O erythrocytes with a strong preference for group A. Agglutinates bovine erythrocytes with a very low specificity (PubMed:19100814, PubMed:22298779). Binds carbohydrates bivalently, which is required for its biological activity (PubMed:22298779). Exhibits insecticidal activity against the fruit fly D.melanogaster, mosquito A.aegypti, and amoebozoa A.castellanii. Has anti-nutritional activity against Colorado potato beetle L.decemlineata, and against worm C.elegans (PubMed:21556921, PubMed:21486374). Has antiproliferative activity against human leukemic T-cells (PubMed:19100814). Has an immunostimulatory effect on human antigen-presenting dendritic cells, which are subsequently able to induce efficient T-cell immune responses (PubMed:22044067).[1] [2] [3] [4] [5] Publication Abstract from PubMedLectins are carbohydrate-binding proteins that exert their biological activity by binding to specific cell glycoreceptors. We have expressed CNL, a ricin B-like lectin from the basidiomycete Clitocybe nebularis, in Escherichia coli. The recombinant lectin, rCNL, agglutinates human blood group A erythrocytes and is specific for the unique glycan N,N'-diacetyllactosediamine (GalNAcbeta1-4GlcNAc, LacdiNAc, LDN) as demonstrated by glycan microarray analysis. We here describe the crystal structures of rCNL in complex with lactose and LDN, defining its interactions with the sugars. CNL is a homodimeric lectin, each of whose monomers comprises a single ricin B lectin domain with its beta-trefoil fold and one carbohydrate-binding site. In order to study the mode of CNL action, a non-sugar-binding mutant and non-dimerizing monovalent mutants that retain carbohydrate-binding activity were prepared. rCNL and the mutants were examined for their biological activities against Jurkat human leukemic T cells and the hypersensitive nematode Caenorhabditis elegans mutant strain pmk-1. rCNL was toxic against both, while the mutants were inactive. Thus, the bivalent carbohydrate-binding property of homodimeric CNL is essential for its activity, providing one of the rare pieces of evidence that certain activities of lectins are associated with their multivalency. Bivalent carbohydrate binding is required for biological activity of CNL, the LacdiNAc (GalNAcbeta1-4GlcNAc)-specific lectin from basidiomycete Clitocybe nebularis.,Pohleven J, Renko M, Magister S, Smith DF, Kuenzler M, Strukelj B, Turk D, Kos J, Sabotic J J Biol Chem. 2012 Feb 1. PMID:22298779[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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