Protein Domain : IPR019565

Type:  Domain Name:  Alpha-2-macroglobulin, thiol-ester bond-forming
Description:  This entry contains serum complement C3 and C4 precursors and alpha-macrogrobulins. The alpha-macroglobulin (aM) family of proteins includes protease inhibitors [], 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 inhibitorymechanism 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 []. 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 [] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation []. Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified [, ].This short highly conserved region of proteinase-binding alpha-macro-globulins contains the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved. Short Name:  MacrogloblnA2_thiol-ester-bond

0 Child Features

1 Contains

DB identifier Type Name
IPR019742 Conserved_site Alpha-2-macroglobulin, conserved site

1 Cross References

Identifier
PF10569

1 Found In

DB identifier Type Name
IPR008930 Domain Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid

0 GO Annotation

0 Ontology Annotations

0 Parent Features

1 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
56571 C1DZE0 PAC:27396884 Micromonas sp RCC299 1594  

6 Publications

First Author Title Year Journal Volume Pages PubMed ID
            2473064
            2472396
            2469470
            2430968
            9914899
            10426429