Characterization of human pregnancy zone protein. Comparison with human alpha 2-macroglobulin.
Native human pregnancy zone protein (PZP), a close homolog of alpha 2-macroglobulin (alpha 2M), can be obtained in approximately 20% yield from pooled late pregnancy plasma or serum by a combination of polyethylene glycol precipitation, euglobulin precipitation, DEAE-Sephacel chromatography, zinc-chelate affinity chromatography, and negative affinity chromatography on insolubilized antibodies against human serum proteins. Both proteins are similarly organized as disulfide-bridged dimers of 360 kDa containing 180-kDa subunits. These dimers constitute the proteinase-binding units of PZP, and in contrast to alpha 2M, they appear to be only loosely associated, indicating a subtle difference in the quaternary structure of these alpha-macroglobulins. The preparations contain functionally intact beta-cysteinyl-gamma-glutamyl thiol esters, located in the same nonapeptide sequence as found in alpha 2M, and form complexes with a variety of proteinases in which a large fraction of the proteinase is bound covalently. Proteinases bound to PZP are still active and poorly accessible to reaction with large inhibitors like alpha 1-proteinase inhibitor. The structural and functional features of PZP indicate that PZP and alpha 2M, although extremely similar, may have different yet overlapping sets of proteinases as targets. It is possible that PZP mainly controls the activity of cellular proteinases released under conditions of increased cellular turnover and that PZP could be the human equivalent to the acute phase alpha-macroglobulins known in other species.
Sand
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Folkersen
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Westergaard
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JG
Sottrup-Jensen
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D011232:Chemical Precipitation; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D004220:Disulfides / Q000032:analysis; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D011092:Polyethylene Glycols; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000032:analysis*; D015032:Zinc; D000511:alpha-Macroglobulins / Q000032:analysis*
D004220:Disulfides; D046911:Macromolecular Substances; D011257:Pregnancy Proteins; D000511:alpha-Macroglobulins; D011092:Polyethylene Glycols; D010450:Endopeptidases; D015032:Zinc