5duy
Structure of lectin from the sea mussel Crenomytilus grayanus
Structural highlights
FunctionLEC_CREGR Galactose-binding lectin (PubMed:23886951, PubMed:27010847, PubMed:28636877, PubMed:9568372). Binds both alpha and beta anomer of galactose (Gal), but has a stronger interaction with the glycans having alpha Gal at the non-reducing end and binds beta Gal weakly only in highly branched glycans. Has high affinity to Galalpha1-4Galbeta1-4GlcNAc (PubMed:28636877). Binds N-acetyl-2-deoxy-2-amino-galactose (2-deoxy-GalNAc) (PubMed:23886951, PubMed:9568372). Binds N-acetylgalactosamine (GalNAc) (PubMed:26439416). Binds porcine stomach mucin (PSM) with high affinity (PubMed:26439416, PubMed:30486373). Binds galactosamine (PubMed:27010847). Binds laminin, bovine submaxillary mucin (BSM), fibronectin, type I collagen and gelatin with a decreasing affinity, respectively (Ref.3). Has hemagglutinating activity towards human type A erythrocytes (PubMed:26439416, PubMed:9568372, Ref.3). Also hemagglutinates human type 0, B and AB erythrocytes as well as rabbit and mouse erythrocytes (PubMed:9568372). Agglutinates both Gram-positive and Gram-negative bacteria including B.subtilis ATCC 6633, S.aureus ATCC 21027 and E.coli 3254, respectively. No agglutination activity towards Gram-positive S.amurskyense CMM 3673. Has bacteriostatic activity on S.amurskyense CMM 3673, B.subtilis ATCC 6633, S.aureus ATCC 21027 and E.coli 3254. However, has no agglutination nor bacteriostatic activity on Gram-negative C.scophthalmum CIP 104199 or A.troitsensis KMM 3674 (PubMed:23886951). Inhibits growth of fungi from the genera Aspergillus, Penicillium, Trichoderma and st. Mycelia. Inhibits germination of spores and hyphal growth of them (PubMed:25482060). Has dose-dependent cytotoxic effect on the human globotriaosylceramide (Gb3)-expressing Burkitt's lymphoma (Raji) cell line. Binds to Gb3 in these cells leading to activation of caspase-9/3 and PARP (PubMed:28636877). Has dose-dependent cytotoxic effect on the Gb3-expressing human MCF-7 breast cancer cell line (PubMed:27010847). No cytotoxic effect on myelogenous leukemia K562 cell line, which does not express Gb3 (PubMed:28636877). Activates immune responses in mice and increases cytokine production of TNF-alpha, IL-6 and MCP-1 in the serum and the peritoneal lavage of mice. Induces TNF-alpha and IL-6 secretion in mouse RAW264.7 macrophages, mouse bone marrow-derived macrophages, human THP-1 macrophages, human peripheral blood mononuclear cells (PBMCs) and human blood monocyte-derived macrophages. TNF-alpha production in macrophages could not be inhibited by GalNAc, GalN or Gal, indicating that induced cytokine production is separate from its sugar binding activity. Increases intracellular reactive oxygen species levels, expression and phosphorylation of protein kinases PKC alpha/delta, expression of COX-2 and NF-kappaB, and activates the MAPK pathway by increasing the phosphorylation of ERK1/2, JNK1/2 and p38 in mouse RAW264.7 macrophages. Induces endotoxin tolerance in lipopolysaccharide(LPS)-activated macrophages by down-regulating IRAK2 expression, reducing JNK1/2 phosphorylation and NF-kappaB activation. Can slightly increase the bactericidal activity of RAW264.7 macrophages (PubMed:28740170). Has DNA-binding activity (PubMed:27010847). Recognizes pathogen-associated molecular patterns (PAMPs) and binds to LPS from E.coli, but has only little binding to beta-1,3-glucan from E.gracilis and peptidoglycan from S.aureus. Activates secretion of TNF-alpha and IFN-gamma by the human peripheral blood cells (HPBCs) (PubMed:31905927). May be involved in innate immunity acting as an antibacterial and antifungal agent involved in the recognition and clearance of pathogens (PubMed:23886951, PubMed:25482060, PubMed:31905927).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] Publication Abstract from PubMedCGL is a 150 amino-acid residue lectin that was originally isolated from the sea mussel Crenomytilus grayanus. It is specific for binding GalNAc/Gal-containing carbohydrate moieties and in general does not share sequence homology with other known galectins or lectins. Since CGL displays antibacterial, antifungal and antiviral activities, and interacts with high affinity with mucin-type receptors, which are abundant on some cancer cells, knowledge of its structure is of significant interest. Conditions have been established for the expression, purification and crystallization of a recombinant variant of CGL. The crystal structure of recombinant CGL was determined and refined at a resolution of 2.12 A. The amino-acid sequence of CGL contains three homologous regions (73% similarity) and the folded protein has a beta-trefoil topology. Structural comparison of CGL with the closely related lectin MytiLec allowed description of the glycan-binding pockets. Structure of a lectin from the sea mussel Crenomytilus grayanus (CGL).,Jakob M, Lubkowski J, O'Keefe BR, Wlodawer A Acta Crystallogr F Struct Biol Commun. 2015 Nov 1;71(Pt 11):1429-36. doi:, 10.1107/S2053230X15019858. Epub 2015 Oct 24. PMID:26527272[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
