Concanavalin A

Like most lectins, ConA is a homotetramer: each sub-unit (26.5kDa, 235 amino-acids, heavily glycated) binds a metallic atom (usually Mn²⁺ and a Ca²⁺). It has the D₂ symmetry. Its tertiary structure has been elucidated,{{cite journal | vauthors = Min W, Dunn AJ, Jones DH | title = Non-glycosylated recombinant pro-concanavalin A is active without polypeptide cleavage | journal = The EMBO Journal | volume = 11 | issue = 4 | pages = 1303–1307 | date = April 1992 | pmid = 1563347 | pmc = 556578 | doi = 10.1002/j.1460-2075.1992.tb05174.x }} as have the molecular basis of its interactions with metals as well as its affinity for the sugars mannose and glucose{{cite journal | vauthors = Loris R, Hamelryck T, Bouckaert J, Wyns L | title = Legume lectin structure | journal = Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | volume = 1383 | issue = 1 | pages = 9–36 | date = March 1998 | pmid = 9546043 | doi = 10.1016/S0167-4838(97)00182-9 }} are well known.

ConA binds specifically α-D-mannosyl and α-D-glucosyl residues (two hexoses differing only in the alcohol on carbon 2) in terminal position of ramified structures from B-Glycans (rich in α-mannose, or hybrid and bi-antennary glycan complexes). It has 4 binding sites, corresponding to the 4 sub-units. The molecular weight is 104–112 kDa and the isoelectric point (pI) is in the range of 4.5–5.5.

ConA can also initiate cell division (mitogenesis), primarily acting on T-lymphocytes, by stimulating their energy metabolism within seconds of exposure.{{cite journal | vauthors = Krauss S, Buttgereit F, Brand MD | title = Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1412 | issue = 2 | pages = 129–138 | date = June 1999 | pmid = 10393256 | doi = 10.1016/S0005-2728(99)00058-4 | doi-access = free }}

{{for|biotechnological uses|Fluorescent glucose biosensors}}

ConA and its variants (found in closely related plants) are the only proteins known to undergo a post-translational sequence arrangement known as Circular permutation in proteins whereby the N-terminal half of the conA precursor is swapped to become the C-terminal half in the mature form; all other known circular permutations occur at the genetic level.{{cite journal | vauthors = Carrington DM, Auffret A, Hanke DE | title = Polypeptide ligation occurs during post-translational modification of concanavalin A | journal = Nature | year = 1985 | volume = 313 | issue = 5997 | pages = 64–67 | pmid = 3965973 | doi = 10.1038/313064a0 | bibcode = 1985Natur.313...64C | s2cid = 4359482 }}{{cite journal | vauthors = Hendrix RW | title = Protein carpentry | journal = Current Biology | volume = 1 | issue = 2 | pages = 71–73 | date = April 1991 | pmid = 15336168 | doi = 10.1016/0960-9822(91)90280-a | s2cid = 45963307 }} ConA circular permutation is carried out by jack bean asparaginyl endopeptidase,{{cite journal | vauthors = Nonis SG, Haywood J, Schmidberger JW, Mackie ER, Soares da Costa TP, Bond CS, Mylne JS | title = Structural and biochemical analyses of concanavalin A circular permutation by jack bean asparaginyl endopeptidase | journal = The Plant Cell | volume = 33 | issue = 8 | pages = 2794–2811 | date = August 2021 | pmid = 34235541 | doi = 10.1093/plcell/koab130 | pmc = 8408470 }} a versatile enzyme capable of cleaving and ligating peptide substrates at a single active site.{{cite journal | vauthors = Nonis SG, Haywood J, Mylne JS | title = Plant asparaginyl endopeptidases and their structural determinants of function | journal = Biochemical Society Transactions | volume = 49 | issue = 2 | pages = 965–976 | date = April 2021 | pmid = 33666219 | doi = 10.1042/BST20200908 | pmc = 8106488 }} To convert conA to the mature form, jack bean asparaginyl endopeptidase cleaves the precursor of conA in the middle and ligates the two original termini.

Concanavalin A interacts with diverse receptors containing mannose carbohydrates, notably rhodopsin, blood group markers, insulin receptors,{{cite journal | vauthors = Cuatrecasas P, Tell GP | title = Insulin-like activity of concanavalin A and wheat germ agglutinin--direct interactions with insulin receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 70 | issue = 2 | pages = 485–489 | date = February 1973 | pmid = 4510292 | pmc = 433288 | doi = 10.1073/pnas.70.2.485 | doi-access = free | bibcode = 1973PNAS...70..485C | jstor = 62526 }} the immunoglobulins and the carcino-embryonary antigen (CEA). It also interacts with lipoproteins.{{cite journal | vauthors = Harmony JA, Cordes EH | title = Interaction of human plasma low density lipoprotein with concanavalin A and with ricin | journal = The Journal of Biological Chemistry | volume = 250 | issue = 22 | pages = 8614–8617 | date = November 1975 | pmid = 171260 | doi = 10.1016/S0021-9258(19)40714-X | doi-access = free }}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }}

ConA strongly agglutinates erythrocytes irrespective of blood-group, and various cancerous cells.{{cite journal | vauthors = Betton GR | title = Agglutination reactions of spontaneous canine tumour cells, induced by concanavalin A, demonstrated by an isotopic assay | journal = International Journal of Cancer | volume = 18 | issue = 5 | pages = 687–696 | date = November 1976 | pmid = 992901 | doi = 10.1002/ijc.2910180518 | s2cid = 36612952 }}{{cite journal | vauthors = Kakizoe T, Komatsu H, Niijima T, Kawachi T, Sugimura T | title = Increased agglutinability of bladder cells by concanavalin A after administration of carcinogens | journal = Cancer Research | volume = 40 | issue = 6 | pages = 2006–2009 | date = June 1980 | pmid = 7371036 }}{{cite journal | vauthors = Becker FF, Shurgin A | title = Concanavalin A agglutination of cells from primary hepatocellular carcinomas and hepatic nodules induced by N-2-fluorenylacetamide | journal = Cancer Research | volume = 35 | issue = 10 | pages = 2879–2883 | date = October 1975 | pmid = 168971 }} It was demonstrated that transformed cells and trypsin-treated normal cells do not agglutinate at 4 °C, thereby suggesting that there is a temperature-sensitive step involved in ConA-mediated agglutination.{{cite journal | vauthors = Inbar M, Ben-Bassat H, Sachs L | title = A specific metabolic activity on the surface membrane in malignant cell-transformation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 11 | pages = 2748–2751 | date = November 1971 | pmid = 4330939 | pmc = 389516 | doi = 10.1073/pnas.68.11.2748 | doi-access = free | bibcode = 1971PNAS...68.2748I | jstor = 61219 }}{{cite journal | vauthors = Sela BA, Lis H, Sharon N, Sachs L | title = Quantitation of N-acetyl-D-galactosamine-like sites on the surface membrane of normal and transformed mammalian cells | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 249 | issue = 2 | pages = 564–568 | date = December 1971 | pmid = 4332414 | doi = 10.1016/0005-2736(71)90132-5 }}

ConA-mediated agglutination of other cell types has been reported, including muscle cells,{{cite journal | vauthors = Gartner TK, Podleski TR | title = Evidence that a membrane bound lectin mediates fusion of L6 myoblasts | journal = Biochemical and Biophysical Research Communications | volume = 67 | issue = 3 | pages = 972–978 | date = December 1975 | pmid = 1201086 | doi = 10.1016/0006-291X(75)90770-6 }} B-lymphocytes (through surface immunoglobulins),{{cite journal | vauthors = de Petris S | title = Concanavalin A receptors, immunoglobulins, and theta antigen of the lymphocyte surface. Interactions with concanavalin A and with Cytoplasmic structures | journal = The Journal of Cell Biology | volume = 65 | issue = 1 | pages = 123–146 | date = April 1975 | pmid = 1092699 | pmc = 2111157 | doi = 10.1083/jcb.65.1.123 }} fibroblasts,{{cite journal | vauthors = Noonan KD, Burger MM | title = The relationship of concanavalin A binding to lectin-initiated cell agglutination | journal = The Journal of Cell Biology | volume = 59 | issue = 1 | pages = 134–142 | date = October 1973 | pmid = 4201706 | pmc = 2110924 | doi = 10.1083/jcb.59.1.134 }} rat thymocytes,{{cite journal | vauthors = Capo C, Garrouste F, Benoliel AM, Bongrand P, Ryter A, Bell GI | title = Concanavalin-A-mediated thymocyte agglutination: a model for a quantitative study of cell adhesion | journal = Journal of Cell Science | volume = 56 | pages = 21–48 | date = August 1982 | pmid = 7166565 | doi = 10.1242/jcs.56.1.21 }} human fetal (but not adult) intestinal epithelial cells,{{cite journal | vauthors = Weiser MM | title = Concanavalin A agglutination of intestinal cells from the human fetus | journal = Science | volume = 177 | issue = 4048 | pages = 525–526 | date = August 1972 | pmid = 5050484 | doi = 10.1126/science.177.4048.525 | s2cid = 23661797 | bibcode = 1972Sci...177..525W }} and adipocytes.{{cite journal | vauthors = Cuatrecasas P | title = Interaction of wheat germ agglutinin and concanavalin A with isolated fat cells | journal = Biochemistry | volume = 12 | issue = 7 | pages = 1312–1323 | date = March 1973 | pmid = 4696755 | doi = 10.1021/bi00731a011 }}

ConA is a lymphocyte mitogen. Similar to phytohemagglutinin (PHA), it is a selective T cell mitogen relative to its effects on B cells. PHA and ConA bind and cross-link components of the T cell receptor, and their ability to activate T cells is dependent on expression of the T cell receptor.{{cite journal | vauthors = Weiss A, Shields R, Newton M, Manger B, Imboden J | title = Ligand-receptor interactions required for commitment to the activation of the interleukin 2 gene | journal = Journal of Immunology | volume = 138 | issue = 7 | pages = 2169–2176 | date = April 1987 | doi = 10.4049/jimmunol.138.7.2169 | pmid = 3104454 | s2cid = 35173412 | url = http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=3104454 | doi-access = free }}{{cite journal | vauthors = Kanellopoulos JM, De Petris S, Leca G, Crumpton MJ | title = The mitogenic lectin from Phaseolus vulgaris does not recognize the T3 antigen of human T lymphocytes | journal = European Journal of Immunology | volume = 15 | issue = 5 | pages = 479–486 | date = May 1985 | pmid = 3873340 | doi = 10.1002/eji.1830150512 | s2cid = 21414006 }}

ConA interacts with the surface mannose residues of many microbes, including the bacteria E. coli,{{cite journal | vauthors = Ofek I, Mirelman D, Sharon N | title = Adherence of Escherichia coli to human mucosal cells mediated by mannose receptors | journal = Nature | volume = 265 | issue = 5595 | pages = 623–625 | date = February 1977 | pmid = 323718 | doi = 10.1038/265623a0 | s2cid = 4223466 | bibcode = 1977Natur.265..623O }} and Bacillus subtilis{{cite journal | vauthors = Doyle RJ, Birdsell DC | title = Interaction of concanavalin A with the cell wall of Bacillus subtilis | journal = Journal of Bacteriology | volume = 109 | issue = 2 | pages = 652–658 | date = February 1972 | pmid = 4621684 | pmc = 285189 | doi = 10.1128/JB.109.2.652-658.1972 }} and the protist Dictyostelium discoideum.{{cite journal | vauthors = West CM, McMahon D | title = Identification of concanavalin A receptors and galactose-binding proteins in purified plasma membranes of Dictyostelium discoideum | journal = The Journal of Cell Biology | volume = 74 | issue = 1 | pages = 264–273 | date = July 1977 | pmid = 559679 | pmc = 2109878 | doi = 10.1083/jcb.74.1.264 }}

It has also been shown as a stimulator of several matrix metalloproteinases (MMPs).{{cite journal | vauthors = Yu M, Sato H, Seiki M, Thompson EW | title = Complex regulation of membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation by concanavalin A in MDA-MB-231 human breast cancer cells | journal = Cancer Research | volume = 55 | issue = 15 | pages = 3272–3277 | date = August 1995 | pmid = 7614461 }}

ConA has proven useful in applications requiring solid-phase immobilization of glycoenzymes, especially those that have proved difficult to immobilize by traditional covalent coupling. Using ConA-couple matrices, such enzymes may be immobilized in high quantities without a concurrent loss of activity or stability. Such noncovalent ConA-glycoenzyme couplings may be relatively easily reversed by competition with sugars or at acidic pH. If necessary for certain applications, these couplings can be converted to covalent bindings by chemical manipulation.{{cite journal | vauthors = Saleemuddin M, Husain Q | title = Concanavalin A: a useful ligand for glycoenzyme immobilization--a review | journal = Enzyme and Microbial Technology | volume = 13 | issue = 4 | pages = 290–295 | date = April 1991 | pmid = 1367163 | doi = 10.1016/0141-0229(91)90146-2 }}

A report from Taiwan (2009) demonstrated potent therapeutic effect of ConA against experimental hepatoma (liver cancer); in the study by Lei and Chang,{{cite journal | vauthors = Lei HY, Chang CP | title = Lectin of Concanavalin A as an anti-hepatoma therapeutic agent | journal = Journal of Biomedical Science | volume = 16 | pages = 10 | date = January 2009 | issue = 1 | pmid = 19272170 | pmc = 2644972 | doi = 10.1186/1423-0127-16-10 | doi-access = free }} ConA was found to be sequestered more by hepatic tumor cells, in preference to surrounding normal hepatocytes. Internalization of ConA occurs preferentially to the mitochondria after binding to cell membrane glycoproteins, which triggers an autophagic cell death. ConA was found to partially inhibit tumor nodule growth independent of its lymphocyte activation; the eradication of the tumor in the murine in-situ hepatoma model in this study was additionally attributed to the mitogenic/lymphoproliferative action of ConA that may have activated a CD8+ T-cell-mediated, as well as NK- and NK-T cell-mediated, immune response in the liver.

ConA intravitreal injection can be used in the modeling of proliferative vitreoretinopathy in rats.{{cite journal | vauthors = Erdiakov AK, Tikhonovich MV, Rzhavina EM, Gavrilova SA | title = [The characteristics of retina at the development of proliferative vitreoretinopathy in rats after intraocular injection of concanavalin a and dispase] | journal = Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova | volume = 101 | issue = 5 | pages = 572–585 | date = May 2015 | pmid = 26263683 }}{{cite journal | vauthors = Tikhonovich MV, Erdiakov AK, Gavrilova SA | title = Nonsteroid anti-inflammatory therapy suppresses the development of proliferative vitreoretinopathy more effectively than a steroid one | journal = International Ophthalmology | volume = 38 | issue = 4 | pages = 1365–1378 | date = August 2018 | pmid = 28639085 | doi = 10.1007/s10792-017-0594-3 | s2cid = 4017540 }}

{{Reflist|30em}}

{{Commons category|Canavalin}}

• {{MeshName|Concanavalin+A}}
• {{MeshName|Concanavalin+A+Receptors}}
• [http://www.life.uiuc.edu/crofts/bioph354/bergman/1cvn/e1cvnm.htm Concanavalin A structure] {{Webarchive|url=https://web.archive.org/web/20080820103956/http://www.life.uiuc.edu/crofts/bioph354/bergman/1cvn/e1cvnm.htm |date=2008-08-20 }}
• [https://web.archive.org/web/20080905174252/http://plab.ku.dk/tcbh/lectin-links.htm World of Lectin, Gateway to lectins]
• {{Proteopedia|1bxh}} con A in complex with methyl alpha1-2 mannobioside

{{Lectins}}

Category:Proteins

Category:Lectins

Category:Legume lectins