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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2001
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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. |
format | Text |
id | pubmed-2198817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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