2P9R
Human alpha2-macroglogulin is composed of multiple domains, as predicted by homology with complement component C3
2P9R の概要
エントリーDOI | 10.2210/pdb2p9r/pdb |
分子名称 | Alpha-2-macroglobulin (2 entities in total) |
機能のキーワード | human alpha2-macroglobulin, mg2 domain, signaling protein |
由来する生物種 | Homo sapiens (human) |
細胞内の位置 | Secreted: P01023 |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 23348.49 |
構造登録者 | |
主引用文献 | Doan, N.,Gettins, P.G. Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3. Biochem.J., 407:23-30, 2007 Cited by PubMed Abstract: Human alpha2M (alpha2-macroglobulin) and the complement components C3 and C4 are thiol ester-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 alpha2M 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 alpha2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the alpha2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of alpha2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1-MG8 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 alpha2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of alpha2M, 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. PubMed: 17608619DOI: 10.1042/BJ20070764 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.3 Å) |
構造検証レポート
検証レポート(詳細版)
をダウンロード
