Major basic protein explained

Eosinophil major basic protein, often shortened to major basic protein (MBP; also called Proteoglycan 2 (PRG2)) is encoded in humans by the PRG2 gene.^[1]

Function

The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helmintho-toxin, and in immune hypersensitivity reactions. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases.^[1]

PRG2 is a 117-residue protein that predominates in eosinophil granules. It is a potent enzyme against helminths and is toxic towards bacteria and mammalian cells in vitro. The eosinophil major basic protein also causes the release of histamine from mast cells and basophils, and activates neutrophils and alveolar macrophages.

Structure

Structurally the major basic protein (MBP) is similar to lectins (sugar-binding proteins), and has a fold similar to that seen in C-type lectins. However, unlike other C-type lectins (those that bind various carbohydrates in the presence of calcium), MBP does not bind either calcium or any of the other carbohydrates that this family recognize.

Instead, MBP recognises heparan sulfate proteoglycans. Two crystallographic structures of MBP have been determined.^{[2] [3]}

Interactions

Major basic protein has been shown to interact with Pregnancy-associated plasma protein A.^{[4] [5] [6]}

See also

• Arylsulfatase

Further reading

• Vanhaesebroeck B, Alessi DR . The PI3K-PDK1 connection: more than just a road to PKB . Biochem. J. . 346 . 3. 561–76 . 2000 . 10698680 . 10.1042/0264-6021:3460561. 1220886 .
• Yoshimatsu K . Purification and cDNA cloning of a novel factor produced by a human T-cell hybridoma: sequence homology with animal lectins . Mol. Immunol. . 29 . 4 . 537–546 . 1992 . 1565101 . 10.1016/0161-5890(92)90012-M . Ohya Y . Shikata Y . Toshio . S . Yoshikazu . H . Isao . T . Tamio . K . Kyousuke . K . Satoshi . T .
• Barker RL . Cloning and sequence analysis of the human gene encoding eosinophil major basic protein . Gene . 86 . 2 . 285–289 . 1990 . 2323577 . 10.1016/0378-1119(90)90292-Y . Loegering DA . Arakawa KC . Pease . Larry R. . Gleich . Gerald J. .
• Gabay JE . Antibiotic proteins of human polymorphonuclear leukocytes . Proc. Natl. Acad. Sci. U.S.A. . 86 . 14 . 5610–5614 . 1989 . 2501794 . 10.1073/pnas.86.14.5610 . 297672 . Scott RW . Campanelli D . Griffith . J . Wilde . C . Marra . MN . Seeger . M . Nathan . CF . 1989PNAS...86.5610G. free .
• Wasmoen TL . Evidence of eosinophil granule major basic protein in human placenta . J. Exp. Med. . 170 . 6 . 2051–2063 . 1990 . 2584934 . 10.1084/jem.170.6.2051 . 2189540 . McKean DJ . Benirschke K . Coulam . CB . Gleich . GJ .
• Barker RL, Gleich GJ, Pease LR . Acidic precursor revealed in human eosinophil granule major basic protein cDNA . J. Exp. Med. . 168 . 4 . 1493–1498 . 1988 . 3171483 . 10.1084/jem.168.4.1493 . 2189086 .
• McGrogan M . Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein . J. Exp. Med. . 168 . 6 . 2295–2308 . 1989 . 3199069 . 10.1084/jem.168.6.2295 . 2189145 . Simonsen C . Scott R . Griffith . J . Ellis . N . Kennedy . J . Campanelli . D . Nathan . C . Gabay . J .
• Wasmoen TL . Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein . J. Biol. Chem. . 263 . 25 . 12559–63 . 1988 . 3410852 . Bell MP . Loegering DA . Gleich . GJ . Prendergast . FG . McKean . DJ . 10.1016/S0021-9258(18)37791-3 . free .
• Weller PF, Ackerman SJ, Smith JA . Eosinophil granule cationic proteins: major basic protein is distinct from the smaller subunit of eosinophil peroxidase . J. Leukoc. Biol. . 43 . 1 . 1–4 . 1988 . 3422083 . 10.1002/jlb.43.1.1. 42464743 .
• Kristensen T . Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA . Biochemistry . 33 . 6 . 1592–1598 . 1994 . 7508748 . 10.1021/bi00172a040 . Oxvig C . Sand O . Hundahl Moeller . Niels Peter . Sottrup-Jensen . Lars .
• Oxvig C, Haaning J, Højrup P, Sottrup-Jensen L . Location and nature of carbohydrate groups in proform of human major basic protein isolated from pregnancy serum . Biochem. Mol. Biol. Int. . 33 . 2 . 329–36 . 1994 . 7524900 .
• Bonno M . Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta . Lab. Invest. . 71 . 4 . 560–6 . 1994 . 7526035 . Oxvig C . Kephart GM . Wagner . JM . Kristensen . T . Sottrup-Jensen . L . Gleich . GJ .
• Li MS . Human eosinophil major basic protein, a mediator of allergic inflammation, is expressed by alternative splicing from two promoters . Biochem. J. . 305 . 3. 921–7 . 1995 . 7531438 . 10.1042/bj3050921. 1136346 . Sun L . Satoh T . Fisher . LM . Spry . CJ .
• Oxvig C . Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma . J. Biol. Chem. . 270 . 23 . 13645–13651 . 1995 . 7539791 . 10.1074/jbc.270.23.13645 . Haaning J . Kristensen L . Wagner . JM . Rubin . I . Stigbrand . T . Gleich . GJ . Sottrup-Jensen . L . free .
• Oxvig C . Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein . J. Biol. Chem. . 268 . 17 . 12243–6 . 1993 . 7685339 . Sand O . Kristensen T . Gleich . GJ . Sottrup-Jensen . L . 10.1016/S0021-9258(18)31378-4 . free .
• Levi-Schaffer F . Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils . Blood . 85 . 9 . 2579–86 . 1995 . 7727786 . 10.1182/blood.V85.9.2579.bloodjournal8592579. Lacy P . Severs NJ . Newman . TM . North . J . Gomperts . B . Kay . AB . Moqbel . R . free .
• Oxvig C, Gleich GJ, Sottrup-Jensen L . Localization of disulfide bridges and free sulfhydryl groups in human eosinophil granule major basic protein . FEBS Lett. . 341 . 2–3 . 213–217 . 1994 . 8137941 . 10.1016/0014-5793(94)80459-1 . 43467769 .
• Shikata Y . Pro-major basic protein has three types of sugar chains at the pro-portion . Biochim. Biophys. Acta . 1163 . 3 . 243–9 . 1993 . 8507662 . 10.1016/0167-4838(93)90158-N . Hayashi Y . Yoshimatsu K . Ohya . Y . Seto . T . Fukushima . K . Yoshida . Y .
• Nittoh T . Cloning of cDNA for rat eosinophil major basic protein . Biochim. Biophys. Acta . 1264 . 3 . 261–4 . 1996 . 8547309 . 10.1016/0167-4781(95)00183-2 . Watanabe M . Okayama H . Misawa . S . Isobe . Y . Hayashi . H . Mue . S . Ohuchi . K .
• Delcommenne M . Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase . Proc. Natl. Acad. Sci. U.S.A. . 95 . 19 . 11211–11216 . 1998 . 9736715 . 10.1073/pnas.95.19.11211 . 21621 . Tan C . Gray V . Rue . L . Woodgett . J . Dedhar . S . 1998PNAS...9511211D. free .

Notes and References

1. Web site: Entrez Gene: PRG2 proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein).

2. Swaminathan GJ, Weaver AJ, Loegering DA, Checkel JL, Leonidas DD, Gleich GJ, Acharya KR . Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity . J. Biol. Chem. . 276 . 28 . 26197–26203 . July 2001 . 11319227 . 10.1074/jbc.M100848200 . free .

3. Swaminathan GJ, Myszka DG, Katsamba PS, Ohnuki LE, Gleich GJ, Acharya KR . Eosinophil-granule major basic protein, a C-type lectin, binds heparin . Biochemistry . 44 . 43 . 14152–14158 . November 2005 . 16245931 . 10.1021/bi051112b .

4. Overgaard . M T . Haaning J . Boldt H B . Olsen I M . Laursen L S . Christiansen M . Gleich G J . Sottrup-Jensen L . Conover C A . Oxvig C . October 2000 . Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor . J. Biol. Chem. . 275 . 40 . 31128–31133 . UNITED STATES. 0021-9258. 10913121 . 10.1074/jbc.M001384200 . free.
5. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C . January 2003 . Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment . J. Biol. Chem. . 278 . 4 . 2106–2117 . United States. 0021-9258. 12421832 . 10.1074/jbc.M208777200 . free .
6. Oxvig . C . Sand O . Kristensen T . Gleich G J . Sottrup-Jensen L . June 1993 . Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein . J. Biol. Chem. . 268 . 17 . 12243–6 . UNITED STATES. 10.1016/S0021-9258(18)31378-4 . 0021-9258. 7685339 . free .