Calcium determines the shape of fibrillin

Dieter P. Reinhard, Diane E. Mechling, Bruce A. Boswell, Douglas R. Keene, Lynn Y. Sakai, Hans Peter Bächinger

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81 Scopus citations

Abstract

Velocity sedimentation experiments using authentic fibrillin-1 demonstrated sedimentation coefficients of s(20,w)/0 = 5.1 ± 0.1 in the Ca2+ form and s(20,w)/0 = 6.2 ± 0.1 in the Ca2+-free form. Calculations based on these results and the corresponding molecular mass predicted a shortening of fibrillin by 25% and an increase in width of 13-17% upon removal of Ca2+. These observations were confirmed by analysis of Ca2+- loaded and Ca2+-free rotary shadowed fibrillin molecules. Analysis of recombinant fibrillin.l subdomain rF17, consisting primarily of an array of 12 Ca2+-binding epidermal growth factor (cbEGF)-like repeats, by analytical ultracentrifugation and rotary shadowing further confirmed Ca2+dependent structural changes in the tertiary structure of fibrillin-1. Based on these results, the contribution of a single cbEGF-like repeat to the length of tandem arrays is predicted to be -3 nm in the Ca2+ form. Ca2+-free forms demonstrated a decrease of 20-30% in length, indicating significant structural changes of these motifs when they occur in tandem. Circular dichroism measurements of rF17 in the presence and absence of Ca2+ indicated secondary structural changes within and adjacent to the interdomain regions that connect cbEGF-like repeats. The results presented here suggest a flexible structure for the Ca2+-free form of fibrillin which becomes stabilized, more extended, and rigid in the Ca2+ form.

Original languageEnglish (US)
Pages (from-to)7368-7373
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number11
DOIs
StatePublished - Mar 14 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Reinhard, D. P., Mechling, D. E., Boswell, B. A., Keene, D. R., Sakai, L. Y., & Bächinger, H. P. (1997). Calcium determines the shape of fibrillin. Journal of Biological Chemistry, 272(11), 7368-7373. https://doi.org/10.1074/jbc.272.11.7368