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PMID: 2412223 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Model of alpha 2-macroglobulin structure and function.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 82 ·No. 17 ·1985-09-00 ·Pages 5700-4

Feldman SR, Gonias SL, Pizzo SV

Abstract

A model of alpha 2-macroglobulin is presented that is compatible with previous structural, functional, and phylogenetic studies of the protein. The model of the molecule resembles a hollow cylinder and is comprised of two identical functional halves with three C2 axes of symmetry and no mirror planes. The "trap mechanism" of this proteinase inhibitor is effected by slight movement of two trap arms per "half-molecule." Evidence for this model is obtained from the study of the structure and proteinase binding of the molecule. By using this model, predictions are made concerning proteinase binding ratios, receptor recognition, and "slow-to-fast" conformational change of the molecule.

MeSH Terms
Animals Chymotrypsin/antagonists & inhibitors,metabolism Fibrinolysin/antagonists & inhibitors,metabolism Humans Kinetics Macromolecular Substances Microscopy, Electron Models, Structural Protease Inhibitors Protein Binding Protein Conformation Structure-Activity Relationship alpha-Macroglobulins
Chemicals
Macromolecular Substances Protease Inhibitors alpha-Macroglobulins Chymotrypsin Fibrinolysin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Feldman S R
Gonias S L
Pizzo S V
References (34)
34 references, click to expand
  1. Structure and function of haemoglobin. 3. A three-dimensional fourier synthesis of human deoxyhaemoglobin at 5.5 Angstrom resolution.
    J Mol Biol. 1967 Aug 28;28(1):117-56 PMID: 6051747
  2. A thiol-ester in alpha 2-macroglobulin cleaved during proteinase complex formation.
    FEBS Lett. 1980 Dec 1;121(2):275-9 PMID: 6161841
  3. Uptake of proteinase-alpha-macroglobulin complexes by macrophages.
    Biochim Biophys Acta. 1975 Dec 5;411(2):295-304 PMID: 1201282
  4. Immunoglobulin structure and effector functions.
    Immunochemistry. 1978 Sep;15(9):695-714 PMID: 367955
  5. The electrophoretically 'slow' and 'fast' forms of the alpha 2-macroglobulin molecule.
    Biochem J. 1979 Aug 1;181(2):401-18 PMID: 91367
  6. Characterization of alkylamine-sensitive site in alpha 2-macroglobulin.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4313-6 PMID: 92026
  7. Localization of the two protease binding sites in human alpha 2-macroglobulin.
    J Biol Chem. 1981 Jan 25;256(2):547-50 PMID: 6161127
  8. Clearance and binding of two electrophoretic "fast" forms of human alpha 2-macroglobulin.
    J Biol Chem. 1981 Aug 10;256(15):8134-9 PMID: 6167573
  9. A monoclonal antibody to a neo-antigen on alpha 2-macroglobulin complexes inhibits receptor-mediated endocytosis.
    J Immunol. 1981 Nov;127(5):1782-6 PMID: 6170673
  10. Further characterization of the covalent linking reaction of alpha 2-macroglobulin.
    Biochem J. 1981 May 1;195(2):453-61 PMID: 6172116
  11. Catabolic pathways for streptokinase, plasmin, and streptokinase activator complex in mice. In vivo reaction of plasminogen activator with alpha 2-macroglobulin.
    J Clin Invest. 1982 Aug;70(2):412-23 PMID: 6178757
  12. Computer averaging of single molecules of alpha 2-macroglobulin and the alpha 2-macroglobulin/trypsin complex.
    Hoppe Seylers Z Physiol Chem. 1982 Aug;363(8):803-12 PMID: 6180967
  13. Evolution of alpha 2-macroglobulin. The structure of a protein homologous with human alpha 2-macroglobulin from plaice (Pleuronectes platessa L.) plasma.
    Biochem J. 1982 Jul 1;205(1):105-15 PMID: 6181776
  14. Evolution of alpha 2-macroglobulin. The demonstration in a variety of vertebrate species of a protein resembling human alpha 2-macroglobulin.
    Biochem J. 1982 Jul 1;205(1):91-5 PMID: 6181778
  15. Physical properties of human alpha 2-macroglobulin following reaction with methylamine and trypsin.
    Biochim Biophys Acta. 1982 Aug 10;705(3):306-14 PMID: 6181812
  16. Residual alpha 2-macroglobulin in fetal calf serum and properties of its complex with thrombin.
    Biochem Biophys Res Commun. 1982 Aug 31;107(4):1243-51 PMID: 6182882
  17. Interaction of alpha 2-macroglobulin with trypsin, chymotrypsin, plasmin, and papain.
    Arch Biochem Biophys. 1983 Feb 15;221(1):261-70 PMID: 6187288
  18. Localization of the proteinase-induced thiol groups in alpha 2-macroglobulin.
    Biochem Biophys Res Commun. 1983 Mar 29;111(3):964-9 PMID: 6188466
  19. Characterization of functional human alpha 2-macroglobulin half-molecules isolated by limited reduction with dithiothreitol.
    Biochemistry. 1983 Feb 1;22(3):536-46 PMID: 6188480
  20. Ligand binding, conformational change and plasma elimination of human, mouse and rat alpha-macroglobulin proteinase inhibitors.
    Biochem J. 1983 Jan 1;209(1):99-105 PMID: 6189480
  21. In vitro binding and in vivo clearance of human alpha 2-macroglobulin after reaction with endoproteases from four different classes.
    Biochem Biophys Res Commun. 1983 Jul 29;114(2):757-62 PMID: 6192823
  22. Reaction of human alpha 2-macroglobulin half-molecules with plasmin as a probe of protease binding site structure.
    Biochemistry. 1983 Oct 11;22(21):4933-40 PMID: 6196052
  23. Interaction of human plasmin with human alpha 2-macroglobulin.
    Biochemistry. 1984 Jan 3;23(1):105-11 PMID: 6197993
  24. Identification of "embryonin" as bovine alpha 2-macroglobulin.
    J Biol Chem. 1984 Apr 10;259(7):4458-62 PMID: 6200483
  25. The primary structure of alpha 2-macroglobulin and localization of a Factor XIIIa cross-linking site.
    Ann N Y Acad Sci. 1983;421:41-60 PMID: 6202214
  26. Chemical and structural modifications of alpha 2-macroglobulin: effects on receptor binding and endocytosis studied in an in vivo model.
    Ann N Y Acad Sci. 1983;421:457-71 PMID: 6202219
  27. Structure of alpha 2-macroglobulin in solution and its interaction with proteases: an X-ray scattering study using the contrast variation method.
    Ann N Y Acad Sci. 1983;421:98-111 PMID: 6202225
  28. Changes in the binding of "fast"-form alpha 2-macroglobulin to 3T3-L1 cells after differentiation to adipocytes.
    Biochemistry. 1984 Jul 17;23(15):3395-403 PMID: 6205689
  29. Circular dichroic spectroscopy of non-human alpha-macroglobulins.
    Biochem Biophys Res Commun. 1984 Sep 17;123(2):771-7 PMID: 6207818
  30. Comparison of the binding of chicken alpha-macroglobulin and ovomacroglobulin to the mammalian alpha 2-macroglobulin receptor.
    Arch Biochem Biophys. 1984 Nov 15;235(1):267-75 PMID: 6208849
  31. Fluorescent probes as a measure of conformational alterations induced by nucleophilic modification and proteolysis of bovine alpha 2-macroglobulin.
    Biochemistry. 1984 Dec 18;23(26):6679-85 PMID: 6085010
  32. Binding of alpha 2-macroglobulin to hepatocytes: mechanism of in vivo clearance.
    Biochem Biophys Res Commun. 1985 Apr 30;128(2):795-802 PMID: 2581569
  33. Purification and characterization of frog alpha-macroglobulin: receptor recognition of an amphibian glycoprotein.
    Biochemistry. 1985 May 7;24(10):2569-75 PMID: 2410015
  34. The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism.
    Biochem J. 1973 Aug;133(4):709-24 PMID: 4201304
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.82.17.5700
Published
1985-09-00
Pages
5700-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC390619
Subset
IM
Grants
NCI NIH HHS · CA-29589 · United States
NIGMS NIH HHS · GM-07171 · United States
NHLBI NIH HHS · HL-24066 · United States
External Links
PubMed source DOI: 10.1073/pnas.82.17.5700 PMC Full Text View journal details
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