User:Cboursnell/Sandbox/A2M recep
| A2M_recep | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 receptor domain from alpha-2-macroglobulin | |||||||||
| Identifiers | |||||||||
| Symbol | A2M_recep | ||||||||
| Pfam | PF07677 | ||||||||
| InterPro | IPR009048 | ||||||||
| PROSITE | PDOC00440 | ||||||||
| SCOP2 | 1bv8 / SCOPe / SUPFAM | ||||||||
| |||||||||
This entry represents the receptor-binding domain (RBD) of alpha-2-macroglobulin proteins. The RBD is located at the C terminus, its structure having an immunoglobulin-like fold consists of a sandwich of nine strands in two sheets with a Greek-key topology.[1][2]
The alpha-macroglobulin (aM) family of proteins includes protease inhibitors,[3] typified by the human tetrameric a2-macroglobulin (a2M); they belong to the MEROPS proteinase inhibitor family I39, clan IL. These protease inhibitors share several defining properties, which include (i) the ability to inhibit proteases from all catalytic classes, (ii) the presence of a 'bait region' and a thiol ester, (iii) a similar protease inhibitory mechanism and (iv) the inactivation of the inhibitory capacity by reaction of the thiol ester with small primary amines. aM protease inhibitors inhibit by steric hindrance.[4] The mechanism involves protease cleavage of the bait region, a segment of the aM that is particularly susceptible to proteolytic cleavage, which initiates a conformational change such that the aM collapses about the protease. In the resulting aM-protease complex, the active site of the protease is sterically shielded, thus substantially decreasing access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) the h-cysteinyl-g-glutamyl thiol ester becomes highly reactive and (ii) a major conformational change exposes a conserved COOH-terminal receptor binding domain [5] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation.[6] Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified.[7][8]
References[edit]
- ^ Xiao T, DeCamp DL, Spran SR (October 2000). "Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer". Protein Sci. 9 (10): 1889–1897. doi:10.1110/ps.9.10.1889. PMC 2144472. PMID 11106161.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Jenner L, Husted L, Thirup S, Sottrup-Jensen L, Nyborg J (May 1998). "Crystal structure of the receptor-binding domain of alpha 2-macroglobulin". Structure. 6 (5): 595–604. doi:10.1016/s0969-2126(98)00061-6. PMID 9634697.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Sottrup-Jensen L (July 1989). "Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation". J. Biol. Chem. 264 (20): 11539–11542. doi:10.1016/S0021-9258(18)80094-1. PMID 2473064.
{{cite journal}}: CS1 maint: date and year (link) - ^ Enghild JJ, Salvesen G, Thøgersen IB, Pizzo SV (July 1989). "Proteinase binding and inhibition by the monomeric alpha-macroglobulin rat alpha 1-inhibitor-3". J. Biol. Chem. 264 (19): 11428–11435. doi:10.1016/S0021-9258(18)60482-X. PMID 2472396.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Enghild JJ, Thøgersen IB, Roche PA, Pizzo SV (February 1989). "A conserved region in alpha-macroglobulins participates in binding to the mammalian alpha-macroglobulin receptor". Biochemistry. 28 (3): 1406–1412. doi:10.1021/bi00429a069. PMID 2469470.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Van Leuven F, Cassiman JJ, Van den Berghe H (December 1986). "Human pregnancy zone protein and alpha 2-macroglobulin. High-affinity binding of complexes to the same receptor on fibroblasts and characterization by monoclonal antibodies". J. Biol. Chem. 261 (35): 16622–16625. doi:10.1016/S0021-9258(18)66612-8. PMID 2430968.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Dodds AW, Law SK (December 1998). "The phylogeny and evolution of the thioester bond-containing proteins C3, C4 and alpha 2-macroglobulin". Immunol. Rev. 166: 15–26. doi:10.1111/j.1600-065x.1998.tb01249.x. PMID 9914899.
{{cite journal}}: CS1 maint: date and year (link) - ^ Armstrong PB, Quigley JP (1999). "Alpha2-macroglobulin: an evolutionarily conserved arm of the innate immune system". Dev. Comp. Immunol. 23 (4–5): 375–390. doi:10.1016/s0145-305x(99)00018-x. PMID 10426429.