We propose a new model for the alignment of fibrillin molecules within fibrillin microfibrils. Automated electron tomography was used to generate three-dimensional microfibril reconstructions to 18.6-Å resolution, which revealed many new organizational details of untensioned microfibrils, including heart-shaped beads from which two arms emerge, and interbead diameter variation. Antibody epitope mapping of untensioned microfibrils revealed the juxtaposition of epitopes at the COOH terminus and near the proline-rich region, and of two internal epitopes that would be 42-nm apart in unfolded molecules, which infers intramolecular folding. Colloidal gold binds microfibrils in the absence of antibody. Comparison of colloidal gold and antibody binding sites in untensioned microfibrils and those extended in vitro, and immunofluorescence studies of fibrillin deposition in cell layers, indicate conformation changes and intramolecular folding. Mass mapping shows that, in solution, microfibrils with periodicities of <70 and >140 nm are stable, but periodicities of ∼100 nm are rare. Microfibrils comprise two in-register filaments with a longitudinal symmetry axis, with eight fibrillin molecules in cross section. We present a model of fibrillin alignment that fits all the data and indicates that microfibril extensibility follows conformation-dependent maturation from an initial head-to-tail alignment to a stable approximately one-third staggered arrangement.
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5 March 2001
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March 05 2001
The Supramolecular Organization of Fibrillin-Rich Microfibrils
Clair Baldock,
Clair Baldock
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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Abraham J. Koster,
Abraham J. Koster
bDepartment of Molecular and Cell Biology, Universiteit Utrecht, 3584 CH Utrecht, The Netherlands
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Ulrike Ziese,
Ulrike Ziese
bDepartment of Molecular and Cell Biology, Universiteit Utrecht, 3584 CH Utrecht, The Netherlands
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Matthew J. Rock,
Matthew J. Rock
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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Michael J. Sherratt,
Michael J. Sherratt
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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Karl E. Kadler,
Karl E. Kadler
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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C. Adrian Shuttleworth,
C. Adrian Shuttleworth
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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Cay M. Kielty
Cay M. Kielty
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
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Clair Baldock
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
Abraham J. Koster
bDepartment of Molecular and Cell Biology, Universiteit Utrecht, 3584 CH Utrecht, The Netherlands
Ulrike Ziese
bDepartment of Molecular and Cell Biology, Universiteit Utrecht, 3584 CH Utrecht, The Netherlands
Matthew J. Rock
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
Michael J. Sherratt
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
Karl E. Kadler
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
C. Adrian Shuttleworth
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
Cay M. Kielty
aWellcome Trust Centre for Cell-Matrix Research, Schools of Biological Sciences and Medicine, University of Manchester, Manchester, M13 9PT, United Kingdom
Abbreviations used in this paper: 3-D, three dimensional; AET, automated electron tomography; MUL, mass per unit length; STEM, scanning transmission electron microscopy; TB, TGF-β binding protein like.
Received:
September 25 2000
Revision Requested:
December 11 2000
Accepted:
January 18 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Cell Biol (2001) 152 (5): 1045–1056.
Article history
Received:
September 25 2000
Revision Requested:
December 11 2000
Accepted:
January 18 2001
Connected Content
Citation
Clair Baldock, Abraham J. Koster, Ulrike Ziese, Matthew J. Rock, Michael J. Sherratt, Karl E. Kadler, C. Adrian Shuttleworth, Cay M. Kielty; The Supramolecular Organization of Fibrillin-Rich Microfibrils. J Cell Biol 5 March 2001; 152 (5): 1045–1056. doi: https://doi.org/10.1083/jcb.152.5.1045
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