Andersen G R, Koch T J, Dolmer K, Sottrup-Jensen L, Nyborg J
Department of Chemistry, University of Aarhus, Denmark.
J Biol Chem. 1995 Oct 20;270(42):25133-41. doi: 10.1074/jbc.270.42.25133.
The structure of methylamine-treated human alpha 2-macroglobulin (alpha 2M-Ma), a 720-kDa tetrameric inactivated proteinase inhibitor from plasma, has been determined to a resolution of 10 A. Data were collected with synchrotron radiation at 120 K, and phases were calculated by multiple isomorphous replacement and solvent flattening. A novel feature of the structure of alpha 2-M is present in its proteinase-binding cavity, dividing it into two compartments. The potential sites for proteinase entrapment in these compartments are sterically restricted. The positions of the thiol groups appearing from the functional important thiol esters upon their cleavage have been determined. They are found at the walls of the compartments at the center of the structure. The overall structure of alpha 2M-MA is much more sphere-like than previously inferred from electron microscopy studies. However, several aspects of the structure are well described by recent three-dimensional reconstructions. Possible models for the monomer, the disulfide bridged dimer, and native alpha 2M are discussed.
甲胺处理过的人α2-巨球蛋白（α2M-Ma）的结构已被测定，分辨率达10埃。α2M-Ma是一种来自血浆的720 kDa的四聚体失活蛋白酶抑制剂。数据在120 K下用同步辐射收集，相位通过多重同晶置换和溶剂扁平化计算得出。α2-M结构的一个新特征出现在其蛋白酶结合腔中，该腔被分成两个隔室。这些隔室中蛋白酶截留的潜在位点在空间上受到限制。已确定了功能性重要硫醇酯裂解后出现的硫醇基团的位置。它们位于结构中心隔室的壁上。α2M-MA的整体结构比以前从电子显微镜研究中推断的更像球形。然而，最近的三维重建很好地描述了该结构的几个方面。讨论了单体、二硫键桥接二聚体和天然α2M的可能模型。
