The following text describes a protein:
Function:
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). Has hemolytic activity towards human (A, B and O-type), rabbit and rat erythrocytes, but not towards mouse, chicken or horse erythrocytes. 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. Has hemagglutinating activity towards rabbit, human and rat erythrocytes, and at relatively high concentrations towards chicken and horse erythrocytes, but not towards mouse erythrocytes. 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. 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. Also leads to severely impaired oocyst formation of human malaria parasite P.falciparum in transgenic mosquitoes fed on mature P.falciparum gametocyte cultures. May be involved in defense mechanisms acting as a toxic protein to foreign microorganisms. May act in defense against predators.
Subcellular Localization:
Secreted.
Domain:
The N-terminal part (1-293) is a carbohydrate recognition domain (CRD) having three ricin B-type lectin domains with two carbohydrate-binding domains. The CRD domain comprises of residues 11-159 and 160-293 and each of them has a beta-trefoil fold. Total of five carbohydrate molecules are bound by the CRD domain. The CRD domain is sufficient for N-acetylgalactosamine (GalNAc)-binding. The CRD domain has weak hemagglutinating activity towards rabbit erythrocytes in the presence or absence of Ca(2+), but it is abolished in the presence of 10 mM EDTA or by lactose; The C-terminal part (291-442) is essential for oligomerization. Oligomerization of the C-terminal part is induced upon binding of lactose. This C-terminal part is able to cause hemagglutination of rabbit erythrocytes probably due to hydrophobic interaction of the oligomer with the membrane leading to formation of ion-permeable pores in the membrane. Hemagglutinating activity of it is not inhibited by lactose, it is enhanced by Ca(2+) and completeely abolished in the presence of 10 mM EDTA; C-terminal part (342-361) has antibacterial activity especially toward Gram-positive bacteria S.aureus IFO 12732, and to a lesser extent toward Gram-positive bacteria B.subtilis IFO 3134. Weak antibacterial activity toward Gram-negative bacteria P.aeruginosa ATCC 27853, and even weaker toward Gram-negative bacteria E.coli ATCC 43827. This C-terminal part disrupts the bacterial membrane leading to enhanced permeabilization of the bacterial membrane. It has membrane-permeabilizing activity also in artificial lipid vesicles.
Sequence:
MVSLVPCGFAQVLCTNPLDIGELRNYKSKQCVDIVGNQGSGNIATHDCDGLSDQQIIMCGDGTIRNEARNYCFTPDGSGNANVMSSPCTLYPEIPSSQRWRLGRKKAFTDNGGIEQVATEIINLASGKCLDVEGSDGTGDIGVYDCQNLDDQYFYIRSRGPELFYGRLRNEKSDLCLDVEGSEGKGNVLMYSCEDNLDQWFRYYENGEIVNAKQGMCLDVEGSDGSGNVGIYRCDDLRDQMWSRPNAYCNGDYCSFLNKESNKCLDVSGDQGTGDVGTWQCDGLPDQRFKWVFDDWEVPTATWNMVGCDQNGKVSQQISNTISFSSTVTAGVAVEVSSTIEKGVIFAKASVSVKVTASLSKAWTNSQSGTTAITYTCDNYDSDEEFTRGCMWQLAIETTEVKSGDLLVWNPQIIKCTRSNTAPGCAPFTKCANEDCTFCTDI