| Structural highlights
Function
CEL3_CUCEC Galactose/N-acetylgalactosamine (Gal/GalNAc)-binding lectin with hemolytic activity. Favors saccharides that have a beta-1,4 linkage at the non-reducing end rather than saccharides having alpha-1,6 or alpha-1,4 linkages. Binds lactose, lactulose, GalNAc, galactosamine, methyl alpha-galactopyranoside, methyl beta-galactopyranoside, N-acetyllactosamine, p-nitrophenyl beta-D-galactopyranoside (pNP-Gal), p-nitrophenyl N-acetyl-beta-D-galactosaminide (pNP-GalNAc), asialofetuin, and human erythrocyte membrane lipids lactosyl ceramide (LacCer) and globoside globotetraosylceramide (Gb4Cer). Binds moderately to galactose, melibiose, raffinose, fucose, methyl alpha-galactoside and methyl beta-galactoside. Binds weakly to glucose, mannose and N-acetylglucosamine (GlcNAc) (PubMed:10101284, PubMed:10478454, PubMed:10923802, PubMed:11471734, PubMed:11983084, PubMed:14561725, PubMed:15194688, PubMed:17977832, PubMed:18159942, PubMed:19356139, PubMed:19420692, PubMed:22313748, PubMed:23470749, PubMed:23545649, PubMed:23583369, PubMed:24652284, PubMed:27101707, PubMed:7798179, PubMed:7876091, PubMed:8663224, PubMed:9058193, PubMed:9133626, PubMed:9305736, PubMed:9692203, PubMed:9805377, PubMed:9990124). Has hemolytic activity towards human (A, B and O-type), rabbit and rat erythrocytes, but not towards mouse, chicken or horse erythrocytes (PubMed:10101284, PubMed:10923802, PubMed:11471734, PubMed:18159942, PubMed:19356139, PubMed:19420692, PubMed:22313748, PubMed:23583369, PubMed:27101707, PubMed:7798179, PubMed:7876091, PubMed:8663224, PubMed:9058193, PubMed:9692203, PubMed:9805377). Forms ion-permeable transmembrane pores in the erythrocyte membrane as well as in artificial liposomes containing human erythrocyte membrane lipids LacCer, Gb4Cer and galactosyl ceramide (GalCer) leading to destruction of the membrane (PubMed:10478454, PubMed:7876091, PubMed:9133626, PubMed:9990124). Has hemagglutinating activity towards rabbit, human and rat erythrocytes, and at relatively high concentrations towards chicken and horse erythrocytes, but not towards mouse erythrocytes (PubMed:10923802, PubMed:11471734, PubMed:14561725, PubMed:18159942, PubMed:19420692, PubMed:7798179, PubMed:9692203, PubMed:9805377, PubMed:9990124). Has dose-dependent cytotoxic effect on Madin-Darby canine kidney (MDCK), African green monkey kidney (Vero) and human epithelia carcinoma (HeLa) cell lines, but Chinese hamster ovary (CHO), rat sarcoma (XC) and potoroo rat kangaroo kidney (PtK1) cells are highly resistant to the cytotoxic effect of this protein (PubMed:10101284, PubMed:9133626). Impairs malaria parasite development in malaria parasite infected transgenic A.stephensi mosquitoes expressing this protein specifically in their midguts. Binds to ookinetes and leads to strong dose-dependent inhibition of ookinete formation in vitro. Leads to severely impaired oocyst formation and significantly reduced sporozoite production of rodent malaria parasite P.berghei in the salivary glands of the transgenic mosquitoes. The parasite transmission to uninfected mice (vectorial competence) of these mosquitoes is significantly impaired. Leads also to severely impaired oocyst formation of human malaria parasite P.falciparum in transgenic mosquitoes fed on mature P.falciparum gametocyte cultures (PubMed:18159942). May be involved in defense mechanisms acting as a toxic protein to foreign microorganisms (PubMed:7876091, PubMed:9133626). May act in defense against predators (PubMed:24652284).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
CEL-III is a Ca(2+)-dependent hemolytic lectin, isolated from the marine invertebrate Cucumaria echinata. The three-dimensional structure of CEL-III/GalNAc and CEL-III/methyl alpha-galactoside complexes was solved by x-ray crystallographic analysis. In these complexes, five carbohydrate molecules were found to be bound to two carbohydrate-binding domains (domains 1 and 2) located in the N-terminal 2/3 portion of the polypeptide and that contained beta-trefoil folds similar to ricin B-chain. The 3-OH and 4-OH of bound carbohydrate molecules were coordinated with Ca(2+) located at the subdomains 1alpha, 1gamma, 2alpha, 2beta, and 2gamma, simultaneously forming hydrogen bond networks with nearby amino acid side chains, which is similar to carbohydrate binding in C-type lectins. The binding of carbohydrates was further stabilized by aromatic amino acid residues, such as tyrosine and tryptophan, through a stacking interaction with the hydrophobic face of carbohydrates. The importance of amino acid residues in the carbohydrate-binding sites was confirmed by the mutational analyses. The orientation of bound GalNAc and methyl alpha-galactoside was similar to the galactose moiety of lactose bound to the carbohydrate-binding site of the ricin B-chain, although the ricin B-chain does not require Ca(2+) ions for carbohydrate binding. The binding of the carbohydrates induced local structural changes in carbohydrate-binding sites in subdomains 2alpha and 2beta. Binding of GalNAc also induced a slight change in the main chain structure of domain 3, which could be related to the conformational change upon binding of specific carbohydrates to induce oligomerization of the protein.
C-type lectin-like carbohydrate recognition of the hemolytic lectin CEL-III containing ricin-type -trefoil folds.,Hatakeyama T, Unno H, Kouzuma Y, Uchida T, Eto S, Hidemura H, Kato N, Yonekura M, Kusunoki M J Biol Chem. 2007 Dec 28;282(52):37826-35. Epub 2007 Oct 31. PMID:17977832[27]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Oda T, Shinmura N, Nishioka Y, Komatsu N, Hatakeyama T, Muramatsu T. Effect of the hemolytic lectin CEL-III from Holothuroidea Cucumaria echinata on the ANS fluorescence responses in sensitive MDCK and resistant CHO cells. J Biochem. 1999 Apr;125(4):713-20. PMID:10101284 doi:10.1093/oxfordjournals.jbchem.a022341
- ↑ Kouriki-Nagatomo H, Hatakeyama T, Jelokhani-Niaraki M, Kondo M, Ehara T, Yamasaki N. Molecular mechanism for pore-formation in lipid membranes by the hemolytic lectin CEL-III from marine invertebrate Cucumaria echinata. Biosci Biotechnol Biochem. 1999 Jul;63(7):1279-84. PMID:10478454 doi:10.1271/bbb.63.1279
- ↑ Kuwahara H, Funada T, Hatakeyama T, Aoyagi H. Effects of chemical modification of carboxyl groups in the hemolytic lectin CEL-III on its hemolytic and carbohydrate-binding activities. Biosci Biotechnol Biochem. 2000 Jun;64(6):1278-81. PMID:10923802 doi:10.1271/bbb.64.1278
- ↑ Sallay I, Tojo S, Nomiyama K, Kouzuma Y, Kimura M, Yamasaki N. Calcium ions stabilize a protein structure of hemolytic lectin CEL-III from marine invertebrate Cucumaria echinata. Biosci Biotechnol Biochem. 2001 Jun;65(6):1347-52. PMID:11471734 doi:10.1271/bbb.65.1347
- ↑ Kuwahara H, Yamasaki T, Hatakeyama T, Aoyagi H, Fujisawa T. Oligomerization process of the hemolytic lectin CEL-III purified from a sea cucumber, Cucumaria echinata. J Biochem. 2002 May;131(5):751-6. PMID:11983084 doi:10.1093/oxfordjournals.jbchem.a003161
- ↑ Kouzuma Y, Suzuki Y, Nakano M, Matsuyama K, Tojo S, Kimura M, Yamasaki T, Aoyagi H, Hatakeyama T. Characterization of functional domains of the hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata. J Biochem. 2003 Sep;134(3):395-402. PMID:14561725 doi:10.1093/jb/mvg157
- ↑ Uchida T, Yamasaki T, Eto S, Sugawara H, Kurisu G, Nakagawa A, Kusunoki M, Hatakeyama T. Crystal structure of the hemolytic lectin CEL-III isolated from the marine invertebrate Cucumaria echinata: implications of domain structure for its membrane pore-formation mechanism. J Biol Chem. 2004 Aug 27;279(35):37133-41. Epub 2004 Jun 11. PMID:15194688 doi:10.1074/jbc.M404065200
- ↑ Hatakeyama T, Unno H, Kouzuma Y, Uchida T, Eto S, Hidemura H, Kato N, Yonekura M, Kusunoki M. C-type lectin-like carbohydrate recognition of the hemolytic lectin CEL-III containing ricin-type -trefoil folds. J Biol Chem. 2007 Dec 28;282(52):37826-35. Epub 2007 Oct 31. PMID:17977832 doi:http://dx.doi.org/10.1074/jbc.M705604200
- ↑ Yoshida S, Shimada Y, Kondoh D, Kouzuma Y, Ghosh AK, Jacobs-Lorena M, Sinden RE. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development. PLoS Pathog. 2007 Dec;3(12):e192. PMID:18159942 doi:10.1371/journal.ppat.0030192
- ↑ Hisamatsu K, Unno H, Goda S, Hatakeyama T. Roles of the valine clusters in domain 3 of the hemolytic lectin CEL-III in its oligomerization and hemolytic abilities. Protein Pept Lett. 2009;16(4):411-4. PMID:19356139 doi:10.2174/092986609787848054
- ↑ Hisamatsu K, Unno H, Goda S, Hatakeyama T. Effects of Ca2+ on refolding of the recombinant hemolytic lectin CEL-III. Biosci Biotechnol Biochem. 2009 May;73(5):1203-5. PMID:19420692 doi:10.1271/bbb.80793
- ↑ Shimizu Y, Yamazaki H, Yoshida S, Yonekura M, Kouzuma Y. Molecular cloning, functional expression, and characterization of isolectin genes of hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata. Biosci Biotechnol Biochem. 2012;76(2):276-82. PMID:22313748 doi:10.1271/bbb.110635
- ↑ Goda S, Sadakata H, Unno H, Hatakeyama T. Effects of detergents on the oligomeric structures of hemolytic lectin CEL-III as determined by small-angle X-ray scattering. Biosci Biotechnol Biochem. 2013;77(3):679-81. PMID:23470749 doi:10.1271/bbb.120981
- ↑ Unno H, Hisamatsu K, Nagao T, Tateya Y, Matsumoto N, Goda S, Hatakeyama T. Crystallization and preliminary crystallographic study of oligomers of the haemolytic lectin CEL-III from the sea cucumber Cucumaria echinata. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Apr 1;69(Pt 4):416-20. PMID:23545649 doi:10.1107/S1744309113004065
- ↑ Hisamatsu K, Nagao T, Unno H, Goda S, Hatakeyama T. Identification of the amino acid residues involved in the hemolytic activity of the Cucumaria echinata lectin CEL-III. Biochim Biophys Acta. 2013 Aug;1830(8):4211-7. PMID:23583369 doi:10.1016/j.bbagen.2013.04.010
- ↑ Unno H, Goda S, Hatakeyama T. Hemolytic lectin CEL-III heptamerizes via a large structural transition from α-helices to a β-barrel during the transmembrane pore formation process. J Biol Chem. 2014 May 2;289(18):12805-12. PMID:24652284 doi:10.1074/jbc.M113.541896
- ↑ Nagao T, Masaki R, Unno H, Goda S, Hatakeyama T. Effects of amino acid mutations in the pore-forming domain of the hemolytic lectin CEL-III. Biosci Biotechnol Biochem. 2016 Oct;80(10):1966-9. PMID:27101707 doi:10.1080/09168451.2016.1176520
- ↑ Hatakeyama T, Kohzaki H, Nagatomo H, Yamasaki N. Purification and characterization of four Ca(2+)-dependent lectins from the marine invertebrate, Cucumaria echinata. J Biochem. 1994 Jul;116(1):209-14. PMID:7798179 doi:10.1093/oxfordjournals.jbchem.a124495
- ↑ Hatakeyama T, Nagatomo H, Yamasaki N. Interaction of the hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata with the erythrocyte membrane. J Biol Chem. 1995 Feb 24;270(8):3560-4. PMID:7876091 doi:10.1074/jbc.270.8.3560
- ↑ Hatakeyama T, Furukawa M, Nagatomo H, Yamasaki N, Mori T. Oligomerization of the hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata induced by the binding of carbohydrate ligands. J Biol Chem. 1996 Jul 12;271(28):16915-20. PMID:8663224 doi:10.1074/jbc.271.28.16915
- ↑ Hatakeyama T, Miyamoto Y, Nagatomo H, Sallay I, Yamasaki N. Carbohydrate-binding properties of the hemolytic lectin CEL-III from the holothuroidea Cucumaria echinata as analyzed using carbohydrate-coated microplate. J Biochem. 1997 Jan;121(1):63-7. PMID:9058193 doi:10.1093/oxfordjournals.jbchem.a021571
- ↑ Oda T, Tsuru M, Hatakeyama T, Nagatomo H, Muramatsu T, Yamasaki N. Temperature from the marine invertebrate Cucumaria echinata on various cell lines. J Biochem. 1997 Mar;121(3):560-7. PMID:9133626 doi:10.1093/oxfordjournals.jbchem.a021622
- ↑ Fujisawa T, Kuwahara H, Hiromasa Y, Niidome T, Aoyagi H, Hatakeyama T. Small-angle X-ray scattering study on CEL-III, a hemolytic lectin from Holothuroidea Cucumaria echinata, and its oligomer induced by the binding of specific carbohydrate. FEBS Lett. 1997 Sep 1;414(1):79-83. PMID:9305736 doi:10.1016/s0014-5793(97)00976-9
- ↑ Hatakeyama T, Matsuyama Y, Funada T, Fukuyama S, Kuwahara H, Aoyagi H, Yamasaki N. Chemical modification of the hemolytic lectin CEL-III by succinic anhydride: involvement of amino groups in the oligomerization process. Biosci Biotechnol Biochem. 1998 Jun;62(6):1185-9. PMID:9692203 doi:10.1271/bbb.62.1185
- ↑ Sallay I, Hatakeyama T, Yamasaki N. Studies on the carbohydrate binding sites of the hemolytic lectin CEL-III isolated from the marine invertebrate Cucumaria echinata. Biosci Biotechnol Biochem. 1998 Sep;62(9):1757-61. PMID:9805377 doi:10.1271/bbb.62.1757
- ↑ Hatakeyama T, Sato T, Taira E, Kuwahara H, Niidome T, Aoyagi H. Characterization of the interaction of hemolytic lectin CEL-III from the marine invertebrate, Cucumaria echinata, with artificial lipid membranes: involvement of neutral sphingoglycolipids in the pore-forming process. J Biochem. 1999 Feb;125(2):277-84. PMID:9990124 doi:10.1093/oxfordjournals.jbchem.a022284
- ↑ Hatakeyama T, Unno H, Kouzuma Y, Uchida T, Eto S, Hidemura H, Kato N, Yonekura M, Kusunoki M. C-type lectin-like carbohydrate recognition of the hemolytic lectin CEL-III containing ricin-type -trefoil folds. J Biol Chem. 2007 Dec 28;282(52):37826-35. Epub 2007 Oct 31. PMID:17977832 doi:http://dx.doi.org/10.1074/jbc.M705604200
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