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The Supramolecular Organization of Fibrillin-Rich Microfibrils

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...

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Detalles Bibliográficos
Autores principales: Baldock, Clair, Koster, Abraham J., Ziese, Ulrike, Rock, Matthew J., Sherratt, Michael J., Kadler, Karl E., Shuttleworth, C. Adrian, Kielty, Cay M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198817/
https://www.ncbi.nlm.nih.gov/pubmed/11238459
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author Baldock, Clair
Koster, Abraham J.
Ziese, Ulrike
Rock, Matthew J.
Sherratt, Michael J.
Kadler, Karl E.
Shuttleworth, C. Adrian
Kielty, Cay M.
author_facet Baldock, Clair
Koster, Abraham J.
Ziese, Ulrike
Rock, Matthew J.
Sherratt, Michael J.
Kadler, Karl E.
Shuttleworth, C. Adrian
Kielty, Cay M.
author_sort Baldock, Clair
collection PubMed
description 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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spelling pubmed-21988172008-05-01 The Supramolecular Organization of Fibrillin-Rich Microfibrils Baldock, Clair Koster, Abraham J. Ziese, Ulrike Rock, Matthew J. Sherratt, Michael J. Kadler, Karl E. Shuttleworth, C. Adrian Kielty, Cay M. J Cell Biol Original Article 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. The Rockefeller University Press 2001-03-05 /pmc/articles/PMC2198817/ /pubmed/11238459 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Baldock, Clair
Koster, Abraham J.
Ziese, Ulrike
Rock, Matthew J.
Sherratt, Michael J.
Kadler, Karl E.
Shuttleworth, C. Adrian
Kielty, Cay M.
The Supramolecular Organization of Fibrillin-Rich Microfibrils
title The Supramolecular Organization of Fibrillin-Rich Microfibrils
title_full The Supramolecular Organization of Fibrillin-Rich Microfibrils
title_fullStr The Supramolecular Organization of Fibrillin-Rich Microfibrils
title_full_unstemmed The Supramolecular Organization of Fibrillin-Rich Microfibrils
title_short The Supramolecular Organization of Fibrillin-Rich Microfibrils
title_sort supramolecular organization of fibrillin-rich microfibrils
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2198817/
https://www.ncbi.nlm.nih.gov/pubmed/11238459
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