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Symmetry of the inhibitory unit of human alpha 2-macroglobulin.

Publication ,  Journal Article
Roche, PA; Salvesen, GS; Pizzo, SV
Published in: Biochemistry
October 4, 1988

Human alpha 2-macroglobulin (alpha 2M) of Mr approximately 720,000 is a proteinase inhibitor whose four identical subunits are arranged to form two adjacent inhibitory units. At present, the spatial arrangement of the two subunits which form one inhibitory unit (the functional "half-molecule") is not known. Treatment of alpha 2M with either 0.5 mM dithiothreitol (DTT) or 4 M urea results in dissociation of the native tetramer into two half-molecules of Mr approximately 360,000. These half-molecules retain trypsin inhibitory activity, but in each case, the reaction results in reassociation of the half-molecules to produce tetramers of Mr approximately 720,000. However, when reacted with plasmin, the preparations of half-molecules have different properties. DTT-induced half-molecules protect the activity of plasmin from inhibition by soybean trypsin inhibitor (STI) without reassociation, while urea-induced half-molecules show no ability to protect plasmin from reaction with STI. High-performance size-exclusion chromatography and sedimentation velocity ultracentrifugation studies were then used to estimate the Stokes radius (Re) of alpha 2M and both DTT- and urea-induced half-molecules of alpha 2M. The Re of tetrameric alpha 2M was 88-94 A, while that of DTT-induced half-molecules was 57-60 A and urea-induced half-molecules 75-77 A. These results demonstrate that DTT- and urea-induced half-molecules have fundamentally different molecular dimensions as well as inhibitory properties. The hydrodynamic data suggest that the urea-induced half-molecule is a "rod"-like structure, although it is not possible to predict the three-dimensional structure of this molecule with the available data.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 4, 1988

Volume

27

Issue

20

Start / End Page

7876 / 7881

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Urea
  • Trypsin Inhibitors
  • Protein Conformation
  • Molecular Weight
  • In Vitro Techniques
  • Humans
  • Fibrinolysin
  • Dithiothreitol
  • Biochemistry & Molecular Biology
 

Citation

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Roche, P. A., Salvesen, G. S., & Pizzo, S. V. (1988). Symmetry of the inhibitory unit of human alpha 2-macroglobulin. Biochemistry, 27(20), 7876–7881. https://doi.org/10.1021/bi00420a044
Roche, P. A., G. S. Salvesen, and S. V. Pizzo. “Symmetry of the inhibitory unit of human alpha 2-macroglobulin.Biochemistry 27, no. 20 (October 4, 1988): 7876–81. https://doi.org/10.1021/bi00420a044.
Roche PA, Salvesen GS, Pizzo SV. Symmetry of the inhibitory unit of human alpha 2-macroglobulin. Biochemistry. 1988 Oct 4;27(20):7876–81.
Roche, P. A., et al. “Symmetry of the inhibitory unit of human alpha 2-macroglobulin.Biochemistry, vol. 27, no. 20, Oct. 1988, pp. 7876–81. Pubmed, doi:10.1021/bi00420a044.
Roche PA, Salvesen GS, Pizzo SV. Symmetry of the inhibitory unit of human alpha 2-macroglobulin. Biochemistry. 1988 Oct 4;27(20):7876–7881.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 4, 1988

Volume

27

Issue

20

Start / End Page

7876 / 7881

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Urea
  • Trypsin Inhibitors
  • Protein Conformation
  • Molecular Weight
  • In Vitro Techniques
  • Humans
  • Fibrinolysin
  • Dithiothreitol
  • Biochemistry & Molecular Biology