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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2006-8-9
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pubmed:abstractText |
Fibrillin-1 is a 330-kDa multidomain extracellular matrix protein that polymerizes to form 57-nm periodic microfibrils, which are essential for all tissue elasticity. Fibrillin-1 is a member of the calcium-binding EGF repeat family and has served as a prototype for structural analyses. Nevertheless, both the detailed structure of fibrillin-1 and its organization within microfibrils are poorly understood because of the complexity of the molecule and the resistance of EGF arrays to crystallization. Here, we have used small-angle x-ray scattering and light scattering to analyze the solution structure of human fibrillin-1 and to produce ab initio structures of overlapping fragments covering 90% of the molecule. Rather than exhibiting a uniform rod shape as current models predict, the scattering data revealed a nonlinear conformation of calcium-binding EGF arrays in solution. This finding has major implications for the structures of the many other EGF-containing extracellular matrix and membrane proteins. The scattering data also highlighted a very compact, globular region of the fibrillin-1 molecule, which contains the integrin and heparan sulfate-binding sites. This finding was confirmed by calculating a 3D reconstruction of this region using electron microscopy and single-particle image analysis. Together, these data have enabled the generation of an improved model for microfibril organization and a previously undescribed mechanism for microfibril extensibility.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-10354416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-10636927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-11238459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-11371467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-12203987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-12511552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-12807887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-12824332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-12871973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15039439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15569675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15649891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15837522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15876369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15923225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-15980072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-16364917,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-1770007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-2512293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-8613981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-8617764,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-8653794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-8742718,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16880403-9724613
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:BaldockClairC,
pubmed-author:BaxDaniel VDV,
pubmed-author:BerryRichardR,
pubmed-author:CainStuart ASA,
pubmed-author:GrossmannJ GünterJG,
pubmed-author:HastonJ LouiseJL,
pubmed-author:KieltyCay MCM,
pubmed-author:MarsonAndrewA,
pubmed-author:MellodyKieran TKT,
pubmed-author:RoessleManfredM,
pubmed-author:SieglerVeroniqueV,
pubmed-author:WangMing-ChuanMC,
pubmed-author:WessTim JTJ
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11922-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16880403-Epidermal Growth Factor,
pubmed-meshheading:16880403-Extracellular Matrix,
pubmed-meshheading:16880403-Heparitin Sulfate,
pubmed-meshheading:16880403-Humans,
pubmed-meshheading:16880403-Image Processing, Computer-Assisted,
pubmed-meshheading:16880403-Kinetics,
pubmed-meshheading:16880403-Microfilament Proteins,
pubmed-meshheading:16880403-Microscopy, Electron,
pubmed-meshheading:16880403-Models, Chemical,
pubmed-meshheading:16880403-Models, Molecular,
pubmed-meshheading:16880403-Molecular Conformation,
pubmed-meshheading:16880403-Nanostructures,
pubmed-meshheading:16880403-Protein Structure, Tertiary
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pubmed:year |
2006
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pubmed:articleTitle |
Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility.
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pubmed:affiliation |
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Greater Manchester M13 9PT, UK. clair.baldock@manchester.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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