Domain

Alpha-macroglobulin, receptor-binding (IPR009048)

Short name: A-macroglobulin_rcpt-bd

Domain relationships

None.

Description

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 [PMID: 11106161, PMID: 9634697].

The alpha-macroglobulin (aM) family of proteins includes protease inhibitors [PMID: 2473064], 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 [PMID: 2472396]. 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 [PMID: 2469470] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation [PMID: 2430968]. Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified [PMID: 9914899, PMID: 10426429].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0005576 extracellular region

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
GENE3D
SMART
Pfam
SUPERFAMILY