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Wheat germ agglutinin

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Wheat germ agglutinin (WGA) is a lectin that protects wheat (Triticum) from insects, yeast and bacteria. An agglutinin protein, it binds to N-acetyl-D-glucosamine and sialic acid.[1] WGA has also been shown to interact with sialic acid residues on oligosaccharides.[2] Succinylated WGA is selective for β-N-acetylglucosamine (β-GlcNAc), making it a useful tool for detecting O-GlcNAc. WGA is composed of a mixture of three isoforms (WGA1, WGA2, WGA3), which are quite similar to each other and each contain an unusually high amount of glycine.[3][4] These three isoforms vary at a total of 10 amino acid positions and all have dimeric structures with four domains per monomer.[3] Each domain (WGA.A, WGA.B, WGA.C, WGA.D) is hevein-like and is stabilized by a disulfide bond.[5] N-acetyl-D-glucosamine in the natural environment of wheat is found in the chitin of insects, and the cell membrane of yeast & bacteria. WGA is found abundantly—but not exclusively—in the wheat kernel, where it got the 'germ' name from. In mammals the N-acetyl-D-glucosamine that WGA binds to is found in cartilage[6] and cornea[7] among other places. In those animals sialic acid is found in mucous membranes, e.g. the lining of the inner nose, and digestive tract.

Agglutinin isolectin 1
Identifiers
OrganismTriticum aestivum
SymbolWGA1
PDB2uvo
UniProtP10968
Search for
StructuresSwiss-model
DomainsInterPro

In solution, WGA exists mostly as a heterodimer of 38,000 daltons. It is cationic at physiological pH. It contains a Carbohydrate-binding module called CBM18.

The above image shows WGA3 in the program Chimera (PDB code 1WGT). The cyan color shows the cysteine residues, the light green color shows the glycine residues, and the dark gray color shows the remaining hydrophobic residues.

Use in molecular biology

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WGA is also widely used in biological research, particularly in the field of glycobiology.[5] Since WGA binds to glycoconjugates, it can be used to label cell membranes,[8] fibrotic scar tissue[9] and arbuscular mycorrhizae[10] for imaging and analysis. WGA is fairly stable in acidic solutions, and can be resistant to proteolysis.[11] WGA has also demonstrated some cytotoxicity and has thus been used in recent research involving hematological cancers, particularly acute myeloid leukemia.[2] In addition, WGA has been thought to improve drug delivery due to its ability to cross the blood-brain barrier, but research has yet to be performed on this hypothesis.[5]

 
A fluorescent microscopy image of a fungal arbuscule stained with WGA and Alexa Fluor

See also

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  • Proteopedia: 2uvo – High resolution crystal structure of Wheat Germ Agglutinin in complex with N-acetyl-D-glucosamine
  • Proteopedia: 2uwg – Crystal structure of Wheat Germ Agglutinin isolectin 1 in complex with glycosylurethan

References

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  1. ^ Monsigny M, Roche AC, Sene C, Maget-Dana R, Delmotte F (February 1980). "Sugar-lectin interactions: how does wheat-germ agglutinin bind sialoglycoconjugates?". European Journal of Biochemistry. 104 (1): 147–53. doi:10.1111/j.1432-1033.1980.tb04410.x. PMID 6892800.
  2. ^ a b Ryva, Bradley; Zhang, Keman; Asthana, Abhishek; Wong, Derek; Vicioso, Yorleny; Parameswaran, Reshmi (2019). "Wheat Germ Agglutinin as a Potential Therapeutic Agent for Leukemia". Frontiers in Oncology. 9: 100. doi:10.3389/fonc.2019.00100. ISSN 2234-943X. PMC 6393371. PMID 30847305.
  3. ^ a b Balčiūnaitė-Murzienė, Gabrielė; Dzikaras, Mindaugas (January 2021). "Wheat Germ Agglutinin—From Toxicity to Biomedical Applications". Applied Sciences. 11 (2): 884. doi:10.3390/app11020884. ISSN 2076-3417.
  4. ^ Allen, A. K.; Neuberger, A.; Sharon, N. (1973-01-01). "The purification, composition and specificity of wheat-germ agglutinin". Biochemical Journal. 131 (1): 155–162. doi:10.1042/bj1310155. ISSN 0264-6021. PMC 1177449. PMID 4737292.
  5. ^ a b c Leyva, Eduardo; Medrano-Cerano, Jorge L.; Cano-Sánchez, Patricia; López-González, Itzel; Gómez-Velasco, Homero; del Río-Portilla, Federico; García-Hernández, Enrique (January 2019). "Bacterial expression, purification and biophysical characterization of wheat germ agglutinin and its four hevein-like domains". Biopolymers. 110 (1): e23242. doi:10.1002/bip.23242. ISSN 0006-3525. PMID 30485415.
  6. ^ Ohno J, Tajima Y, Utsumi N (October 1986). "Binding of wheat germ agglutinin in the matrix of rat tracheal cartilage". The Histochemical Journal. 18 (10): 537–40. doi:10.1007/BF01675194. PMID 3804790. S2CID 25384990.
  7. ^ Marfurt CF (February 1988). "Sympathetic innervation of the rat cornea as demonstrated by the retrograde and anterograde transport of horseradish peroxidase-wheat germ agglutinin". The Journal of Comparative Neurology. 268 (2): 147–60. doi:10.1002/cne.902680202. PMID 3360982. S2CID 23955233.
  8. ^ "Plasma Membrane - US". www.thermofisher.com. Retrieved 2020-01-13.
  9. ^ Emde B, Heinen A, Gödecke A, Bottermann K (December 2014). "Wheat germ agglutinin staining as a suitable method for detection and quantification of fibrosis in cardiac tissue after myocardial infarction". European Journal of Histochemistry. 58 (4): 2448. doi:10.4081/ejh.2014.2448. PMC 4289847. PMID 25578975.
  10. ^ Carotenuto, Gennaro; Genre, Andrea (2020). "Fluorescent Staining of Arbuscular Mycorrhizal Structures Using Wheat Germ Agglutinin (WGA) and Propidium Iodide". Arbuscular Mycorrhizal Fungi. Methods in Molecular Biology. Vol. 2146. pp. 53–59. doi:10.1007/978-1-0716-0603-2_5. hdl:2318/1740844. ISBN 978-1-0716-0602-5. PMID 32415595.
  11. ^ Pellegrina, Chiara Dalla; Perbellini, Omar; Scupoli, Maria Teresa; Tomelleri, Carlo; Zanetti, Chiara; Zoccatelli, Gianni; Fusi, Marina; Peruffo, Angelo; Rizzi, Corrado; Chignola, Roberto (2009-06-01). "Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction". Toxicology and Applied Pharmacology. 237 (2): 146–153. doi:10.1016/j.taap.2009.03.012. ISSN 0041-008X. PMID 19332085.
 

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