Low Resolution X-ray Structure of Human Methylamine-treated -Macroglobulin

• Published in: The Journal of biological chemistry 1995-10, Vol.270 (42), p.25133
• Main Authors: Gregers R. Andersen, Trine J. Koch, Klavs Dolmer, Lars Sottrup-Jensen, Jens Nyborg
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.42.25133

The structure of methylamine-treated human α -macroglobulin (α M-MA), a 720-kDa tetrameric inactivated proteinase inhibitor from plasma, has been determined to a resolution of 10 Å. 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 α 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 α M-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 α M are discussed.