Dimeric ristocetin flocculates proteins, binds to platelets, and mediates von Willebrand factor-dependent agglutination of platelets

J. Paul Scott, Robert R. Montgomery, Gregory S. Retzinger

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Ristocetin in aqueous solution dimerizes with an equilibrium dissociation constant of 5.0 x 10-4 M, i.e. ~1.1 mg ml-1 (Waltho, J. P., and Williams, D. H. (1989) J. Am. Chem. Soc. 111, 2475-2480). At concentrations of about 1.0 mg ml-1 ristocetin flocculates many proteins, lyses platelets and, in the presence of von Willebrand factor, agglutinates both fresh and formalin-fixed platelets. Because ristocetin exists as both monomeric and dimeric species, we sought to determine which of these forms flocculates proteins and agglutinates platelets. We found that: 1) the initial rate of flocculation of certain proteins, 2) the initial rate of agglutination of formalin-fixed platelets, and 3) the binding of ristocetin to formalin-fixed platelets are higher order solely with respect to the concentration of ristocetin dimers. As to the operative mechanism, it appears that bifunctional dimers cross-link proteins that possess multiple copies of a common recognition site. Preliminary evidence indicates that a recognition site is a β-turn of the form X-P-G-X'.

Original languageEnglish (US)
Pages (from-to)8149-8155
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number13
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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