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On the Structure-Function Relationships of the Unique Proteinase Inhibitor Human α2 Macroglobulin

Published online by Cambridge University Press:  02 July 2020

James K. Stoops ,
Steven J. Kolodziej ,
Usman Qazi ,
Norman J. Nolasco ,
Peter G.W. Gettins  and
Dudley K. Strickland
James K. Stoops
Affiliation:
Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX77030
Steven J. Kolodziej
Affiliation:
Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX77030
Usman Qazi
Affiliation:
Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX77030
Norman J. Nolasco
Affiliation:
Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, Houston, TX77030
Peter G.W. Gettins
Affiliation:
Department of Biochemistry and Molecular Biology, University of Illinois, Chicago, IL60612
Dudley K. Strickland
Affiliation:
American Red Cross, 15601 Crabbs Branch Way, Rockville, MD20855
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Extract

Human α2 macroglobulin (α2M) has structural and functional properties that contribute to its uniqueness as proteinase inhibitor. It is the largest known (Mr=720,000) and the only natural proteinase inhibitor which has a broad range of reactivity and for which the reaction is irreversible. It has a vital role in the clearance of proteinases from the circulation and in regulating their activity in fibrinolysis, coagulation and complement activation.

An α2M molecule can entrap two proteinase molecules such as chymotrypsin and trypsin and can therefore be considered to contain two functional domains. Each subunit in the homotetramer has a bait region with cleavage sites for nearly all known endoproteinases and an internal thiol ester bond. A proteinase cleaves the two bait regions within both functional units leading to an activation and cleavage of the thiol ester bonds. Consequently, α2M undergoes a major structural change resulting in the irreversible entrapment of the proteinase.

Type
Proteolysis: A Versatile Biological Control Mechanism
Information
Microscopy and Microanalysis , Volume 4 , Issue S2: Proceedings: Microscopy & Microanalysis '98, Microscopy Society of America 56th Annual Meeting, Microbeam Analysis Society 32nd Annual Meeting, Atlanta, Georgia July 12-16, 1998 , July 1998 , pp. 986 - 987
Copyright
Copyright © Microscopy Society of America

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