title: Evidence for the intramolecular pleating model of fibrillin microfibril organisation from single particle image analysis.
abstract: Fibrillin microfibrils endow mammalian connective tissues with elasticity and are fundamental for the deposition of elastin. The microfibrils are 57nm periodic supramolecular protein polymers with a mass of 2.4MDa per repeat. The detailed structure and organisation of most matrix assemblies is poorly understood due to their large size and complexity and it has proved a major challenge to define their structural organisation. Therefore, we have used low dose electron microscopy and single particle image analysis to study the structure of fibrillin microfibrils. Three novel features were detected: a globular feature that bridges the "arm" region, a double band of density crossing the microfibril and stain penetrating holes present in the interbead region, possibly produced by the removal of microfibril associated proteins in the purification procedure. Fine filaments of approximately 2.4nm diameter are resolved in the interbead region, which correspond to the reported diameter of the fibrillin molecule. Comparison of the stain exclusion pattern of microfibrils with the theoretical stain exclusion pattern of fibrillin packing models indicates that the intramolecular pleating model, where each fibrillin molecule is pleated within one microfibril period allowing extensibility by unpleating, has the best fit to the data.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Lu
authors.forename: David F
authors.initials: DF
authors.lastname: Holmes
authors.forename: Clair
authors.initials: C
authors.lastname: Baldock
mesh_terms: D000818:Animals; D002417:Cattle; D017364:Collagenases; D000071837:Fibrillins; D006821:Hyaluronoglucosaminidase; D020894:Microfibrils / Q000737:chemistry* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000737:chemistry*; D008854:Microscopy, Electron; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D012965:Sodium Chloride
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D012965:Sodium Chloride; D006821:Hyaluronoglucosaminidase; D017364:Collagenases