2p9r
From Proteopedia
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Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3
Overview
Human alpha 2-macroglobulin (alpha 2-M) and the complement components C3, and C4 are thiolester-containing proteins that evolved from the same, ancestral gene. The recent structure determination of human C3 has allowed, a detailed prediction of the location of domains within human alpha 2-M to, be made. We describe here the expression and characterization of three, alpha 2-M domains predicted to be involved in the stabilization of the, thiol ester in native alpha 2-M, and in its activation upon bait region, proteolysis. The three newly-expressed domains are macroglobulin domain 2, (MG2), the thiolester-containing domain (TED) and the CUB domain. Together, with the previously characterized receptor binding domain (RBD) they, represent about 42% of the alpha 2-M polypeptide. Their expression as, folded domains strongly supports the predicted domain organization of, alpha 2-M. An x-ray crystal structure of MG2 shows it to have a, fibronectin 3-type fold analogous to MG domains 1-8 of C3. TED is, as, predicted, an alpha-helical domain. CUB is a spliced domain composed of, two stretches of polypeptide that flank TED in the primary structure. In, intact C3 TED interacts with RBD, where it is in direct contact with the, thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these alpha 2-M domains, as isolated species, show negligible interaction, with one another, suggesting that the native conformation of alpha 2-M, and the consequent thiol ester-stabilizing domain-domain interactions, result from additional restraints imposed by the physical linkage of these, domains or by additional domains in the protein.
About this Structure
2P9R is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Human alpha 2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3., Doan N, Gettins PG, Biochem J. 2007 Jul 4;. PMID:17608619
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