title: Incorporation of non-proteolytic proteins by murine alpha2-macroglobulin.
abstract: Human alpha2-macroglobulin is a tetrameric glycoprotein with a molecular weight of 718 kDa that is present in human plasma at high concentrations. Murine alpha2-macroglobulin is homologous to human alpha2-macroglobulin but it undergoes post-translational cleavage in the subunits. Each subunit of alpha2-macroglobulin contains a thiolester which can be cleaved by small nucleophiles. In human alpha2-macroglobulin this results in a conformational change to a receptor-recognized form and a change in the electrophoretic mobility. Recent work has demonstrated that this process is reversible and during this reversal non-proteolytic proteins can become covalently trapped within the human alpha2-macroglobulin molecule. The present study further investigates this observation and examines the question whether reversal of thiolester cleavage occurs in mouse alpha2-macroglobulin. Previous studies suggest that small nucleophiles only partially convert mouse alpha2-macroglobulin to a receptor-recognized form. We demonstrate here that under appropriate conditions, mouse alpha2-macroglobulin is fully converted by NH3. We also demonstrate that despite structural and kinetic differences between human and mouse alpha2-macroglobulin, both molecules are able to incorporate non-proteolytic ligands in a similar manner. This leads us to propose a general model of ligand incorporation via nucleophilic exchange in multimeric alpha-macroglobulins.
authors.affiliation: Department of Pathology, P.O. Box 3712, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bhattacharjee
authors.forename: H
authors.initials: H
authors.lastname: Grøn
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D000641:Ammonia; D000818:Animals; D006801:Humans; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D000511:alpha-Macroglobulins; D000641:Ammonia