Abstract
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.
References
50
Referenced
133
10.1242/jcs.112.22.4163
/ J. Cell Sci / Regulation of fibrillin carboxy-terminal furin processing by N-glycosylation, and association of amino- and carboxy-terminal sequences by Ashworth (1999)10.1042/bj3400171
/ Biochem. J / Fibrillin degradation by matrix metalloproteinasesimplications for connective tissue remodelling by Ashworth (1999)10.1242/jcs.112.20.3549
/ J. Cell Sci / Fibrillin assemblydimer formation mediated by amino-terminal sequences by Ashworth (1999)10.1006/jmbi.1997.1593
/ J. Mol. Biol. / Metal ion dependency of microfibrils supports a rod-like conformation for fibrillin-1 calcium-binding epidermal growth factor-like domains by Cardy (1998)10.1359/jbmr.2000.15.1.68
/ J. Bone Miner. Res / Role of the latent transforming growth factor beta binding protein 1 in fibrillin-containing microfibrils in bone cells in vitro and in vivo by Dallas (2000)10.1016/S0927-7765(00)00137-5
/ Colloids Surf. B Biointerfaces. / Influence of the water–air interface on the apparent surface tension of aqueous solutions of hydrophilic solutes by Docoslis (2000)10.1016/S0092-8674(00)81259-3
/ Cell. / Solution structure of a pair of calcium binding epidermal growth factor-like domainsimplications for the Marfan syndrome and other genetic disorders by Downing (1996)10.1177/39.1.1983873
/ J. Histochem. Cytochem / Rotary shadowing of collagen monomers, oligomers and fibrils during tendon fibrillogenesis by Fleischmajer (1991)10.1083/jcb.150.3.667
/ J. Cell Biol / New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse by Gayraud (2000)10.1016/S0945-053X(00)00100-1
/ Matrix Biol. / Fibrillinfrom domain structure to supramolecular assembly by Handford (2000)10.1016/S0248-4900(98)80018-X
/ Biol. Cell. / Atomic force microscopy and modelling of natural elastic fibrillin polymers by Hanssen (1998){'key': '2023072211290629000_Hermanson1996', 'volume-title': 'Preparation of colloidal-gold-labelled proteins. In Bioconjugate Techniques', 'author': 'Hermanson', 'year': '1996'}
/ Preparation of colloidal-gold-labelled proteins. In Bioconjugate Techniques by Hermanson (1996)10.1177/39.4.2005373
/ J. Histochem. Cytochem. / Extraction of beaded structures and their identification as fibrillin-containing matrix microfibrils by Keene (1991)10.1242/jcs.99.4.797
/ J. Cell Sci. / Isolation and ultrastructural analysis of microfibrillar structures from foetal bovine elastic tissues. Relative abundance and supramolecular architecture of type VI collagen assemblies and fibrillin by Kielty (1991)10.1016/0014-5793(93)80829-J
/ FEBS Lett. / The role of calcium in the organisation of fibrillin microfibrils by Kielty (1993)10.1016/1357-2725(95)00028-N
/ Int. J. Biochem. Cell Biol. / Fibrillin-containing microfibrils—structure and function in health and disease by Kielty (1995)10.1006/jsbi.1996.0013
/ J. Struct. Biol. / Computer visualisation of three-dimensional image data using IMOD by Kremer (1996)10.1016/S0021-9258(19)30091-2
/ J. Biol. Chem. / Connective tissue microfibrilsIsolation and characterisation of three large pepsin-resistant domains of fibrillin by Maddox (1989)10.1038/352334a0
/ Nature. / Partial sequence of a candidate gene for the Marfan-Syndrome by Maslen (1991)10.1007/978-1-4615-3770-0_4
/ Cell Biology of the Extracellular Matrix / The elastic fiber by Mecham (1991)10.1007/BF01938880
/ Experientia. / The modulus of elasticity of lobster aorta microfibrils by McConnell (1996)10.1093/hmg/2.7.961
/ Hum. Mol. Genet. / Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome by Pereira (1993)10.1016/0014-5793(96)00325-0
/ FEBS Lett / Cell adhesion and integrin binding to recombinant human fibrillin-1 by Pfaff (1996)10.1021/bi971036f
/ Biochemistry. / Alignment of fibrillin molecules in elastic microfibrils is defined by transglutaminase-derived cross-links by Qian (1997)10.1242/jcs.112.7.1093
/ J. Cell Sci / Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE/furin-like activity required for incorporation in the matrix by Raghunath (1999)10.1006/jmbi.1996.0237
/ J. Mol. Biol / Fibrillin-1organisation in microfibrils and structural properties by Reinhardt (1996)10.1074/jbc.272.11.7368
/ J. Biol. Chem. / Calcium determines the shape of fibrillin by Reinhardt (1997)10.1074/jbc.275.16.12339
/ J. Biol. Chem / Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis by Reinhardt (2000)10.1016/1047-8477(91)90062-2
/ J. Struct. Biol. / An analysis by rotary shadowing of the structure of the mammalian vitreous humor and zonular apparatus by Ren (1991)10.1074/jbc.274.13.8933
/ J. Biol. Chem. / Processing of the fibrillin-1 carboxyl-terminal domain by Ritty (1999)10.1136/jmg.37.1.9
/ J. Med. Genet / The molecular genetics of Marfan Syndrome and related microfibrillopathies by Robinson (2000)10.1083/jcb.103.6.2499
/ J. Cell Biol. / Fibrillin, a new 350-kd glycoprotein, is a component of extracellular microfibrils by Sakai (1986)10.1016/S0021-9258(18)98752-1
/ J. Biol. Chem / Purification and partial characterisation of fibrillin, a cysteine-rich structural component of connective tissue microfibrils by Sakai (1991)10.1074/jbc.271.9.4916
/ J. Biol. Chem. / Cell-type specific recognition of RGD- and non–RGD-containing cell binding domains in fibrillin-1 by Sakamoto (1996)10.1006/jsbi.1995.1003
/ Struct. Biol. / Structure of Lumbricus terrestris hemoglobin at 30Å resolution determined using angular reconstitution J by Schatz (1995)10.1016/S1357-2725(97)00028-9
/ Int. J. Biochem. Cell Biol / Scanning transmission electron microscopy mass analysis of fibrillin-containing microfibrils from foetal elastic tissues by Sherratt (1997)10.1016/S0968-4328(99)00082-7
/ Micron. / Fibrillin-rich microfibrils of the extracellular matrixultrastructure and assembly by Sherratt (2001)10.1016/S0945-053X(98)90106-8
/ Matrix Biol. / Cellular and extracellular biology of the latent transforming growth factor-beta binding proteins by Sinha (1998)10.1242/jeb.199.8.1817
/ J. Exp. Biol. / Morphology and biomechanics of the microfibrillar network of sea cucumber dermis by Thurmond (1996)10.3109/03008209709160221
/ Connect. Tissue Res / Partial biochemical and immunologic characterization of fibrillin microfibrils from sea cucumber dermis by Thurmond (1997)10.1042/bj3400693
/ Biochem. J / N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimersa possible first step in microfibril assembly by Trask (1999)10.1091/mbc.11.5.1499
/ Mol. Biol. Cell. / The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin by Trask (2000)10.3109/02713689109007614
/ Curr. Eye Res / Rotary shadowing of elastic system microfibrils in the ocular zonule, vitreous and ligamentum nuchae by Wallace (1991)10.1083/jcb.141.3.829
/ J. Cell Biol. / Calcium determines the supramolecular organization of fibrillin-rich microfibrils by Wess (1998)10.1006/jsbi.1998.3992
/ J. Struct. Biol / X-ray diffraction studies of fibrillin-rich microfibrilseffects of tissue extension on axial and lateral packing by Wess (1998)10.1242/jeb.202.21.3011
/ J. Exp. Biol. / The supramolecular organisation of fibrillin-rich microfibrils determines the mechanical properties of bovine zonular filaments by Wright (1999)10.1016/0889-1605(88)90039-0
/ J. Ultrastruct. Mol. Struct. Res / Vitreous humor of chicken contains two fibrillar systemsan analysis of their structures by Wright (1988)10.1093/emboj/16.22.6659
/ EMBO (Eur. Mol. Biol. Organ.) J. / Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils by Yuan (1997)10.1002/pro.5560071009
/ Prot. Sci. / Effects of proline cis-trans isomerisation on TB domain secondary structure by Yuan (1998)10.1083/jcb.124.5.855
/ J. Cell Biol. / Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices by Zhang (1994)
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 12:46 p.m.) |
Deposited | 2 years, 1 month ago (July 22, 2023, 7:29 a.m.) |
Indexed | 1 month, 3 weeks ago (July 8, 2025, 7:29 a.m.) |
Issued | 24 years, 5 months ago (March 5, 2001) |
Published | 24 years, 5 months ago (March 5, 2001) |
Published Online | 24 years, 5 months ago (March 5, 2001) |
Published Print | 24 years, 5 months ago (March 5, 2001) |
@article{Baldock_2001, title={The Supramolecular Organization of Fibrillin-Rich Microfibrils}, volume={152}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.152.5.1045}, DOI={10.1083/jcb.152.5.1045}, number={5}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Baldock, Clair and Koster, Abraham J. and Ziese, Ulrike and Rock, Matthew J. and Sherratt, Michael J. and Kadler, Karl E. and Shuttleworth, C. Adrian and Kielty, Cay M.}, year={2001}, month=mar, pages={1045–1056} }