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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2002 Feb 28;357(1418):207–217. doi: 10.1098/rstb.2001.1029

Fibrillin: from microfibril assembly to biomechanical function.

Cay M Kielty 1, Clair Baldock 1, David Lee 1, Matthew J Rock 1, Jane L Ashworth 1, C Adrian Shuttleworth 1
PMCID: PMC1692929  PMID: 11911778

Abstract

Fibrillins form the structural framework of a unique and essential class of extracellular microfibrils that endow dynamic connective tissues with long-range elasticity. Their biological importance is emphasized by the linkage of fibrillin mutations to Marfan syndrome and related connective tissue disorders, which are associated with severe cardiovascular, ocular and skeletal defects. These microfibrils have a complex ultrastructure and it has proved a major challenge both to define their structural organization and to relate it to their biological function. However, new approaches have at last begun to reveal important insights into their molecular assembly, structural organization and biomechanical properties. This paper describes the current understanding of the molecular assembly of fibrillin molecules, the alignment of fibrillin molecules within microfibrils and the unique elastomeric properties of microfibrils.

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Selected References

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  1. Ashworth J. L., Kelly V., Rock M. J., Shuttleworth C. A., Kielty C. M. Regulation of fibrillin carboxy-terminal furin processing by N-glycosylation, and association of amino- and carboxy-terminal sequences. J Cell Sci. 1999 Nov;112(Pt 22):4163–4171. doi: 10.1242/jcs.112.22.4163. [DOI] [PubMed] [Google Scholar]
  2. Ashworth J. L., Kelly V., Wilson R., Shuttleworth C. A., Kielty C. M. Fibrillin assembly: dimer formation mediated by amino-terminal sequences. J Cell Sci. 1999 Oct;112(Pt 20):3549–3558. doi: 10.1242/jcs.112.20.3549. [DOI] [PubMed] [Google Scholar]
  3. Ashworth J. L., Kielty C. M., McLeod D. Fibrillin and the eye. Br J Ophthalmol. 2000 Nov;84(11):1312–1317. doi: 10.1136/bjo.84.11.1312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ashworth J. L., Murphy G., Rock M. J., Sherratt M. J., Shapiro S. D., Shuttleworth C. A., Kielty C. M. Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling. Biochem J. 1999 May 15;340(Pt 1):171–181. [PMC free article] [PubMed] [Google Scholar]
  5. Baldock C., Koster A. J., Ziese U., Rock M. J., Sherratt M. J., Kadler K. E., Shuttleworth C. A., Kielty C. M. The supramolecular organization of fibrillin-rich microfibrils. J Cell Biol. 2001 Mar 5;152(5):1045–1056. doi: 10.1083/jcb.152.5.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cardy C. M., Handford P. A. Metal ion dependency of microfibrils supports a rod-like conformation for fibrillin-1 calcium-binding epidermal growth factor-like domains. J Mol Biol. 1998 Mar 13;276(5):855–860. doi: 10.1006/jmbi.1997.1593. [DOI] [PubMed] [Google Scholar]
  7. Cleary E. G., Gibson M. A. Elastin-associated microfibrils and microfibrillar proteins. Int Rev Connect Tissue Res. 1983;10:97–209. doi: 10.1016/b978-0-12-363710-9.50009-5. [DOI] [PubMed] [Google Scholar]
  8. Dallas S. L., Keene D. R., Bruder S. P., Saharinen J., Sakai L. Y., Mundy G. R., Bonewald L. F. Role of the latent transforming growth factor beta binding protein 1 in fibrillin-containing microfibrils in bone cells in vitro and in vivo. J Bone Miner Res. 2000 Jan;15(1):68–81. doi: 10.1359/jbmr.2000.15.1.68. [DOI] [PubMed] [Google Scholar]
  9. Downing A. K., Knott V., Werner J. M., Cardy C. M., Campbell I. D., Handford P. A. Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders. Cell. 1996 May 17;85(4):597–605. doi: 10.1016/s0092-8674(00)81259-3. [DOI] [PubMed] [Google Scholar]
  10. Fleischmajer R., Perlish J. S., Faraggiana T. Rotary shadowing of collagen monomers, oligomers, and fibrils during tendon fibrillogenesis. J Histochem Cytochem. 1991 Jan;39(1):51–58. doi: 10.1177/39.1.1983873. [DOI] [PubMed] [Google Scholar]
  11. Handford P. A., Downing A. K., Reinhardt D. P., Sakai L. Y. Fibrillin: from domain structure to supramolecular assembly. Matrix Biol. 2000 Nov;19(6):457–470. doi: 10.1016/s0945-053x(00)00100-1. [DOI] [PubMed] [Google Scholar]
  12. Keene D. R., Maddox B. K., Kuo H. J., Sakai L. Y., Glanville R. W. Extraction of extendable beaded structures and their identification as fibrillin-containing extracellular matrix microfibrils. J Histochem Cytochem. 1991 Apr;39(4):441–449. doi: 10.1177/39.4.2005373. [DOI] [PubMed] [Google Scholar]
  13. Kielty C. M., Cummings C., Whittaker S. P., Shuttleworth C. A., Grant M. E. Isolation and ultrastructural analysis of microfibrillar structures from foetal bovine elastic tissues. Relative abundance and supramolecular architecture of type VI collagen assemblies and fibrillin. J Cell Sci. 1991 Aug;99(Pt 4):797–807. doi: 10.1242/jcs.99.4.797. [DOI] [PubMed] [Google Scholar]
  14. Kielty C. M., Shuttleworth C. A. Fibrillin-containing microfibrils: structure and function in health and disease. Int J Biochem Cell Biol. 1995 Aug;27(8):747–760. doi: 10.1016/1357-2725(95)00028-n. [DOI] [PubMed] [Google Scholar]
  15. Kielty C. M., Shuttleworth C. A. The role of calcium in the organization of fibrillin microfibrils. FEBS Lett. 1993 Dec 27;336(2):323–326. doi: 10.1016/0014-5793(93)80829-j. [DOI] [PubMed] [Google Scholar]
  16. Kielty C. M., Whittaker S. P., Shuttleworth C. A. Fibrillin: evidence that chondroitin sulphate proteoglycans are components of microfibrils and associate with newly synthesised monomers. FEBS Lett. 1996 May 20;386(2-3):169–173. doi: 10.1016/0014-5793(96)00423-1. [DOI] [PubMed] [Google Scholar]
  17. Lee B., Godfrey M., Vitale E., Hori H., Mattei M. G., Sarfarazi M., Tsipouras P., Ramirez F., Hollister D. W. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991 Jul 25;352(6333):330–334. doi: 10.1038/352330a0. [DOI] [PubMed] [Google Scholar]
  18. Maslen C. L., Corson G. M., Maddox B. K., Glanville R. W., Sakai L. Y. Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991 Jul 25;352(6333):334–337. doi: 10.1038/352334a0. [DOI] [PubMed] [Google Scholar]
  19. McConnell C. J., Wright G. M., DeMont M. E. The modulus of elasticity of lobster aorta microfibrils. Experientia. 1996 Sep 15;52(9):918–921. doi: 10.1007/BF01938880. [DOI] [PubMed] [Google Scholar]
  20. Pereira L., D'Alessio M., Ramirez F., Lynch J. R., Sykes B., Pangilinan T., Bonadio J. Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet. 1993 Jul;2(7):961–968. doi: 10.1093/hmg/2.7.961. [DOI] [PubMed] [Google Scholar]
  21. Raghunath M., Putnam E. A., Ritty T., Hamstra D., Park E. S., Tschödrich-Rotter M., Peters R., Rehemtulla A., Milewicz D. M. Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE/furin-like activity required for incorporation in the matrix. J Cell Sci. 1999 Apr;112(Pt 7):1093–1100. doi: 10.1242/jcs.112.7.1093. [DOI] [PubMed] [Google Scholar]
  22. Raghunath M., Tschödrich-Rotter M., Sasaki T., Meuli M., Chu M. L., Timpl R. Confocal laser scanning analysis of the association of fibulin-2 with fibrillin-1 and fibronectin define different stages of skin regeneration. J Invest Dermatol. 1999 Jan;112(1):97–101. doi: 10.1046/j.1523-1747.1999.00483.x. [DOI] [PubMed] [Google Scholar]
  23. Reinhardt D. P., Gambee J. E., Ono R. N., Bächinger H. P., Sakai L. Y. Initial steps in assembly of microfibrils. Formation of disulfide-cross-linked multimers containing fibrillin-1. J Biol Chem. 2000 Jan 21;275(3):2205–2210. doi: 10.1074/jbc.275.3.2205. [DOI] [PubMed] [Google Scholar]
  24. Reinhardt D. P., Keene D. R., Corson G. M., Pöschl E., Bächinger H. P., Gambee J. E., Sakai L. Y. Fibrillin-1: organization in microfibrils and structural properties. J Mol Biol. 1996 Apr 26;258(1):104–116. doi: 10.1006/jmbi.1996.0237. [DOI] [PubMed] [Google Scholar]
  25. Reinhardt D. P., Mechling D. E., Boswell B. A., Keene D. R., Sakai L. Y., Bächinger H. P. Calcium determines the shape of fibrillin. J Biol Chem. 1997 Mar 14;272(11):7368–7373. doi: 10.1074/jbc.272.11.7368. [DOI] [PubMed] [Google Scholar]
  26. Ren Z. X., Brewton R. G., Mayne R. An analysis by rotary shadowing of the structure of the mammalian vitreous humor and zonular apparatus. J Struct Biol. 1991 Feb;106(1):57–63. doi: 10.1016/1047-8477(91)90062-2. [DOI] [PubMed] [Google Scholar]
  27. Ritty T. M., Broekelmann T., Tisdale C., Milewicz D. M., Mecham R. P. Processing of the fibrillin-1 carboxyl-terminal domain. J Biol Chem. 1999 Mar 26;274(13):8933–8940. doi: 10.1074/jbc.274.13.8933. [DOI] [PubMed] [Google Scholar]
  28. Robinson P. N., Godfrey M. The molecular genetics of Marfan syndrome and related microfibrillopathies. J Med Genet. 2000 Jan;37(1):9–25. doi: 10.1136/jmg.37.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sakai L. Y., Keene D. R., Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986 Dec;103(6 Pt 1):2499–2509. doi: 10.1083/jcb.103.6.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sherratt M. J., Holmes D. F., Shuttleworth C. A., Kielty C. M. Scanning transmission electron microscopy mass analysis of fibrillin-containing microfibrils from foetal elastic tissues. Int J Biochem Cell Biol. 1997 Aug-Sep;29(8-9):1063–1070. doi: 10.1016/s1357-2725(97)00028-9. [DOI] [PubMed] [Google Scholar]
  31. Sherratt M. J., Wess T. J., Baldock C., Ashworth J., Purslow P. P., Shuttleworth C. A., Kielty C. M. Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly. Micron. 2001 Feb;32(2):185–200. doi: 10.1016/s0968-4328(99)00082-7. [DOI] [PubMed] [Google Scholar]
  32. Sinha S., Nevett C., Shuttleworth C. A., Kielty C. M. Cellular and extracellular biology of the latent transforming growth factor-beta binding proteins. Matrix Biol. 1998 Dec;17(8-9):529–545. doi: 10.1016/s0945-053x(98)90106-8. [DOI] [PubMed] [Google Scholar]
  33. Thurmond F, Trotter J. Morphology and biomechanics of the microfibrillar network of sea cucumber dermis. J Exp Biol. 1996;199(Pt 8):1817–1828. doi: 10.1242/jeb.199.8.1817. [DOI] [PubMed] [Google Scholar]
  34. Trask B. C., Trask T. M., Broekelmann T., Mecham R. P. The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin. Mol Biol Cell. 2000 May;11(5):1499–1507. doi: 10.1091/mbc.11.5.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trask T. M., Ritty T. M., Broekelmann T., Tisdale C., Mecham R. P. N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly. Biochem J. 1999 Jun 15;340(Pt 3):693–701. [PMC free article] [PubMed] [Google Scholar]
  36. Unsöld C., Hyytiäinen M., Bruckner-Tuderman L., Keski-Oja J. Latent TGF-beta binding protein LTBP-1 contains three potential extracellular matrix interacting domains. J Cell Sci. 2001 Jan;114(Pt 1):187–197. doi: 10.1242/jcs.114.1.187. [DOI] [PubMed] [Google Scholar]
  37. Wallace R. N., Streeten B. W., Hanna R. B. Rotary shadowing of elastic system microfibrils in the ocular zonule, vitreous, and ligamentum nuchae. Curr Eye Res. 1991 Jan;10(1):99–109. doi: 10.3109/02713689109007614. [DOI] [PubMed] [Google Scholar]
  38. Wess T. J., Purslow P. P., Kielty C. M. Fibrillin-rich microfibrils: an X-ray diffraction study of the fundamental axial periodicity. FEBS Lett. 1997 Aug 25;413(3):424–428. doi: 10.1016/s0014-5793(97)00950-2. [DOI] [PubMed] [Google Scholar]
  39. Wess T. J., Purslow P. P., Kielty C. M. X-Ray diffraction studies of fibrillin-rich microfibrils: effects of tissue extension on axial and lateral packing. J Struct Biol. 1998;122(1-2):123–127. doi: 10.1006/jsbi.1998.3992. [DOI] [PubMed] [Google Scholar]
  40. Wess T. J., Purslow P. P., Sherratt M. J., Ashworth J., Shuttleworth C. A., Kielty C. M. Calcium determines the supramolecular organization of fibrillin-rich microfibrils. J Cell Biol. 1998 May 4;141(3):829–837. doi: 10.1083/jcb.141.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wright D. M., Duance V. C., Wess T. J., Kielty C. M., Purslow P. P. The supramolecular organisation of fibrillin-rich microfibrils determines the mechanical properties of bovine zonular filaments. J Exp Biol. 1999 Nov;202(Pt 21):3011–3020. doi: 10.1242/jeb.202.21.3011. [DOI] [PubMed] [Google Scholar]
  42. Wright D. W., Mayne R. Vitreous humor of chicken contains two fibrillar systems: an analysis of their structure. J Ultrastruct Mol Struct Res. 1988 Sep;100(3):224–234. doi: 10.1016/0889-1605(88)90039-0. [DOI] [PubMed] [Google Scholar]
  43. Yuan X., Downing A. K., Knott V., Handford P. A. Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils. EMBO J. 1997 Nov 17;16(22):6659–6666. doi: 10.1093/emboj/16.22.6659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yuan X., Werner J. M., Knott V., Handford P. A., Campbell I. D., Downing K. Effects of proline cis-trans isomerization on TB domain secondary structure. Protein Sci. 1998 Oct;7(10):2127–2135. doi: 10.1002/pro.5560071009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zhang H., Apfelroth S. D., Hu W., Davis E. C., Sanguineti C., Bonadio J., Mecham R. P., Ramirez F. Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. J Cell Biol. 1994 Mar;124(5):855–863. doi: 10.1083/jcb.124.5.855. [DOI] [PMC free article] [PubMed] [Google Scholar]

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