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Extracellular matrix: from atomic resolution to ultrastructure

Profile image of John VakonakisJohn Vakonakis

2007, Current Opinion in Cell Biology

https://doi.org/10.1016/J.CEB.2007.09.005
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Abstract

The extracellular matrix (ECM) is a highly organized multimolecular structure, essential for life in higher organisms. Although substantial high-resolution structural information is available for relatively small fragments of ECM components, the inherent difficulty in preparing and analyzing samples of large, fibrous polymers impedes structural efforts. Here, we review recent advances in understanding the structure of three important ECM components: collagen, fibrillin and fibronectin. Emphasis is placed on the key role of intermolecular interactions in assembling larger, mm scale, structures.

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References (59)

  1. References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P: Molecular Biology of the Cell. edn 4. London: Garland; 2002.
  3. Werb Z, Chin JR: Extracellular matrix remodeling during morphogenesis. Ann N Y Acad Sci 1998, 857:110-118.
  4. Hohenester E, Engel J: Domain structure and organisation in extracellular matrix proteins. Matrix Biol 2002, 21:115-128.
  5. Laurent TC, Laurent UB, Fraser JR: The structure and function of hyaluronan: An overview. Immunol Cell Biol 1996, 74:A1-A7.
  6. Banerji S, Wright AJ, Noble M, Mahoney DJ, Campbell ID, Day AJ, Jackson DG: Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat Struct Mol Biol 2007, 14:234-239.
  7. Mayo KH: NMR and X-ray studies of collagen model peptides. Biopolymers 1996, 40:359-370.
  8. Brodsky B, Persikov AV: Molecular structure of the collagen triple helix. Adv Protein Chem 2005, 70:301-339.
  9. Okuyama K, Xu X, Iguchi M, Noguchi K: Revision of collagen molecular structure. Biopolymers 2006, 84:181-191.
  10. Kotch FW, Raines RT: Self-assembly of synthetic collagen triple helices. Proc Natl Acad Sci U S A 2006, 103:3028-3033.
  11. Leitinger B, Hohenester E: Mammalian collagen receptors. Matrix Biol 2006, 26:146-155.
  12. An excellent recent review on collagen receptors.
  13. Chapman JA, Hardcastle RA: The staining pattern of collagen fibrils. II. A comparison with patterns computer-generated from the amino acid sequence. Connect Tissue Res 1974, 2:151-159.
  14. Doyle BB, Hulmes DJ, Miller A, Parry DA, Piez KA, Woodhead- Galloway J: Axially projected collagen structures. Proc R Soc Lond B Biol Sci 1974, 187:37-46.
  15. Hulmes DJ, Miller A, Parry DA, Piez KA, Woodhead-Galloway J: Analysis of the primary structure of collagen for the origins of molecular packing. J Mol Biol 1973, 79:137-148.
  16. Steplewski A, Ito H, Rucker E, Brittingham RJ, Alabyeva T, Gandhi M, Ko FK, Birk DE, Jimenez SA, Fertala A: Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils. J Struct Biol 2004, 148:326-337.
  17. See annotation to [16 ].
  18. Steplewski A, Majsterek I, McAdams E, Rucker E, Brittingham RJ, Ito H, Hirai K, Adachi E, Jimenez SA, Fertala A: Thermostability gradient in the collagen triple helix reveals its multi-domain structure. J Mol Biol 2004, 338:989-998.
  19. See annotation to [16 ].
  20. Steplewski A, Hintze V, Fertala A: Molecular basis of organization of collagen fibrils. J Struct Biol 2007, 157:297-307.
  21. Collagen D-periods are shown to have distinguishable domain-like prop- erties, such as thermal stability and tolerance for amino acid substitu- tions. Some of these domain-periods are, however, dispensable for fibril formation. Collectively, these three papers [14 ,15 ,16 ] illustrate the power of recombinant methods in unraveling the structure of a complex system like the collagen fibril.
  22. Bozec L, van der Heijden G, Horton M: Collagen fibrils: nanoscale ropes. Biophys J 2007, 92:70-75.
  23. This study uses AFM on tendon collagen fibrils to show that the observed D-periods can be explained in terms of a spiral arrangement of fibrillar subcomponents, conceptually similar to rope construction.
  24. Orgel JP, Irving TC, Miller A, Wess TJ: Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci U S A 2006, 103:9001-9005.
  25. X-ray fiber diffraction experiments on tendon collagen produced an interpretable low resolution electron density map of crystalline elements in the fibril. Collagen microfibrils interdigitate and adopt a right-handed supertwist along the long axis of the fibril. Intermolecular interactions along the collagen termini maintain the overall packing arrangement.
  26. Hulmes DJ: Building collagen molecules, fibrils, and suprafibrillar structures. J Struct Biol 2002, 137:2-10.
  27. Malone JP, Veis A: Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix receptor. Biochemistry 2004, 43:15358-15366.
  28. Malone JP, George A, Veis A: Type I collagen N-telopeptides adopt an ordered structure when docked to their helix receptor during fibrillogenesis. Proteins 2004, 54:206-215.
  29. Jordan CD, Charbonneau NL, Sakai LY: Fibrillin microfibrils: connective tissue pathways that regulate shape and signaling. J Musculoskelet Interact 2006, 6:366-367.
  30. Whiteman P, Hutchinson S, Handford PA: Fibrillin-1 misfolding and disease. Antioxid Redox Signal 2006, 8:338-346.
  31. Lee SS, Knott V, Jovanovic J, Harlos K, Grimes JM, Choulier L, Mardon HJ, Stuart DI, Handford PA: Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure 2004, 12:717-729.
  32. The crystal structure of the EGF22-TB4-EGF23 fragment of fibrillin-1 shows substantial interdomain interactions mediated by the TB domain. This study suggests that other TB domains in fibrillin may function in a similar role.
  33. Cain SA, Baldock C, Gallagher J, Morgan A, Bax DV, Weiss AS, Shuttleworth CA, Kielty CM: Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. J Biol Chem 2005, 280:30526-30537.
  34. Surface plasmon resonance experiments show the existence of four heparin-binding sites in fibrillin-1. Heparin competes for binding with other fibrillin partners, indicating a likely regulatory role in microfibril assembly.
  35. El-Hallous E, Sasaki T, Hubmacher D, Getie M, Tiedemann K, Brinckmann J, Batge B, Davis EC, Reinhardt DP: Fibrillin-1 interactions with fibulins depend on the first hybrid domain and provide an adaptor function to tropoelastin. J Biol Chem 2007, 282:8935-8946.
  36. Marson A, Rock MJ, Cain SA, Freeman LJ, Morgan A, Mellody K, Shuttleworth CA, Baldock C, Kielty CM: Homotypic fibrillin-1 interactions in microfibril assembly. J Biol Chem 2005, 280:5013-5021.
  37. A solid phase binding assay revealed three homotypic interactions in fibrillin-1, involving the N-and C-termini of the protein. A regulatory role in microfibril assembly is suggested.
  38. Whiteman P, Willis AC, Warner A, Brown J, Redfield C, Handford PA: Cellular and molecular studies of Marfan syndrome mutations identify co-operative protein folding in the cbEGF12-13 region of fibrillin-1. Hum Mol Genet 2007, 16:907-918.
  39. Mellody KT, Freeman LJ, Baldock C, Jowitt TA, Siegler V, Raynal BD, Cain SA, Wess TJ, Shuttleworth CA, Kielty CM: Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological alterations and highlight the structural importance of the second hybrid domain. J Biol Chem 2006, 281:31854-31862.
  40. Handford PA, Downing AK, Reinhardt DP, Sakai LY: Fibrillin: from domain structure to supramolecular assembly. Matrix Biol 2000, 19:457-470.
  41. Lu Y, Sherratt MJ, Wang MC, Baldock C: Tissue specific differences in fibrillin microfibrils analysed using single particle image analysis. J Struct Biol 2006, 155:285-293.
  42. Lu Y, Holmes DF, Baldock C: Evidence for the intramolecular pleating model of fibrillin microfibril organisation from single particle image analysis. J Mol Biol 2005, 349:73-85.
  43. This study shows that the intramolecular 'pleating' model of fibrillin-1 microfibril organization provides the best fit for stain exclusion patterns in EM micrographs. This model was then used to arrange in space single particle reconstructions of fibrillin-1 fragments in [33 ].
  44. Baldock C, Siegler V, Bax DV, Cain SA, Mellody KT, Marson A, Haston JL, Berry R, Wang MC, Grossmann JG et al.: Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility. Proc Natl Acad Sci U S A 2006, 103:11922-11927.
  45. See annotation to [32 ].
  46. Kuo CL, Isogai Z, Keene DR, Hazeki N, Ono RN, Sengle G, Peter Bachinger H, Sakai LY: Effects of fibrillin-1 degradation on microfibril ultrastructure. J Biol Chem 2007, 282:4007- 4020. Analysis of antibody epitopes and collagenase cleavage sites in the fibrillin-1 microfibril monitored by EM supports a staggered model of microfibril organization. Significant differences in the properties of the microfibril were observed depending on the extraction method employed.
  47. Potts JR, Campbell ID: Structure and function of fibronectin modules. Matrix Biol 1996, 15:313-320; discussion 321.
  48. Morla A, Ruoslahti E: A fibronectin self-assembly site involved in fibronectin matrix assembly: reconstruction in a synthetic peptide. J Cell Biol 1992, 118:421-429.
  49. Ingham KC, Brew SA, Huff S, Litvinovich SV: Cryptic self- association sites in type III modules of fibronectin. J Biol Chem 1997, 272:1718-1724.
  50. Aguirre KM, McCormick RJ, Schwarzbauer JE: Fibronectin self- association is mediated by complementary sites within the amino-terminal one-third of the molecule. J Biol Chem 1994, 269:27863-27868.
  51. Hocking DC, Sottile J, McKeown-Longo PJ: Fibronectin's III-1 module contains a conformation-dependent binding site for the amino-terminal region of fibronectin. J Biol Chem 1994, 269:19183-19187.
  52. Litvinovich SV, Ingham KC: Interactions between type III domains in the 110 kDa cell-binding fragment of fibronectin. J Mol Biol 1995, 248:611-626.
  53. Sechler JL, Rao H, Cumiskey AM, Vega-Colon I, Smith MS, Murata T, Schwarzbauer JE: A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly. J Cell Biol 2001, 154:1081-1088.
  54. Oberhauser AF, Badilla-Fernandez C, Carrion-Vazquez M, Fernandez JM: The mechanical hierarchies of fibronectin observed with single-molecule AFM. J Mol Biol 2002, 319:433-447.
  55. Mao Y, Schwarzbauer JE: Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 2005, 24:389-399.
  56. Geiger B, Bershadsky A, Pankov R, Yamada KM: Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2001, 2:793-805.
  57. Erickson HP: Stretching fibronectin. J Muscle Res Cell Motil 2002, 23:575-580.
  58. Erickson HP: Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. Proc Natl Acad Sci U S A 1994, 91:10114-10118.
  59. Ohashi T, Erickson HP: Domain unfolding plays a role in superfibronectin formation. J Biol Chem 2005, 280:39143-39151.

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