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Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system.

Publication ,  Journal Article
Enghild, JJ; Thøgersen, IB; Salvesen, G; Fey, GH; Figler, NL; Gonias, SL; Pizzo, SV
Published in: Biochemistry
October 30, 1990

Significant primary sequence homology between the alpha-macroglobulin family of proteinase inhibitors and the complement components C3, C4, and C5 implies that these proteins arose from a common ancestor. Hemolymph from the ancient invertebrate Limulus polyphemus contains both complement-like and proteinase inhibitory activity. In this report, we present evidence that L. polyphemus alpha-macroglobulin not only possesses proteinase inhibitory activity, but it also participates in the lytic system of the horseshoe crab. The protein is a disulfide-linked dimer of subunits of molecular mass 185 kDa. Upon reaction with proteinase or methylamine, L. polyphemus alpha-macroglobulin underwent a major conformational change and no proteinase-associated multimerization was detected. L. polyphemus alpha-macroglobulin is the only detectable inhibitor of a number of proteinases in L. polyphemus hemolymph. Proteinase inhibition follows the general "trapping" mechanism shared by most alpha-macroglobulins; however, no covalent linking of proteinases to the inhibitor was detected despite the presence of a functional thiolester. Moreover, the inhibitor demonstrated thiolester-mediated binding to sheep erythrocytes, a property also observed with complement components such as C3. Depletion of functional protein by treatment of hemolymph with methylamine destroyed the proteinase inhibitory capacity and the lytic activity of the hemolymph. Both activities were restored by adding purified protein to depleted hemolymph. Studies with purified L. polyphemus alpha-macroglobulin demonstrated that the thiolester incorporates glycerol as well as methylamine, a property shared by human C3. The data support the hypothesis that L. polyphemus alpha-macroglobulin is both a proteinase inhibitor and part of a lytic system, providing a link between the two distinct sides of the alpha-macroglobulin family. Because both properties are contained in one molecule, we propose the name "limac" to describe this Limulus alpha-macroglobulin complement-like protein.

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Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 30, 1990

Volume

29

Issue

43

Start / End Page

10070 / 10080

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Trypsin
  • Sequence Homology, Nucleic Acid
  • Protein Conformation
  • Protease Inhibitors
  • Molecular Sequence Data
  • Horseshoe Crabs
  • Hemolysis
  • Hemolymph
  • Erythrocytes
 

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Enghild, J. J., Thøgersen, I. B., Salvesen, G., Fey, G. H., Figler, N. L., Gonias, S. L., & Pizzo, S. V. (1990). Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system. Biochemistry, 29(43), 10070–10080. https://doi.org/10.1021/bi00495a009
Enghild, J. J., I. B. Thøgersen, G. Salvesen, G. H. Fey, N. L. Figler, S. L. Gonias, and S. V. Pizzo. “Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system.Biochemistry 29, no. 43 (October 30, 1990): 10070–80. https://doi.org/10.1021/bi00495a009.
Enghild JJ, Thøgersen IB, Salvesen G, Fey GH, Figler NL, Gonias SL, et al. Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system. Biochemistry. 1990 Oct 30;29(43):10070–80.
Enghild, J. J., et al. “Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system.Biochemistry, vol. 29, no. 43, Oct. 1990, pp. 10070–80. Pubmed, doi:10.1021/bi00495a009.
Enghild JJ, Thøgersen IB, Salvesen G, Fey GH, Figler NL, Gonias SL, Pizzo SV. Alpha-macroglobulin from Limulus polyphemus exhibits proteinase inhibitory activity and participates in a hemolytic system. Biochemistry. 1990 Oct 30;29(43):10070–10080.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 30, 1990

Volume

29

Issue

43

Start / End Page

10070 / 10080

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Trypsin
  • Sequence Homology, Nucleic Acid
  • Protein Conformation
  • Protease Inhibitors
  • Molecular Sequence Data
  • Horseshoe Crabs
  • Hemolysis
  • Hemolymph
  • Erythrocytes