2ft3 Citations

Crystal structure of the biglycan dimer and evidence that dimerization is essential for folding and stability of class I small leucine-rich repeat proteoglycans.

J Biol Chem 281 13324-13332 (2006)
Cited: 56 times
EuropePMC logo PMID: 16547006

Abstract

Biglycan and decorin are two closely related proteoglycans whose protein cores contain leucine-rich repeats flanked by disulfides. We have previously shown that decorin is dimeric both in solution and in crystal structures. In this study we determined whether biglycan dimerizes and investigated the role of dimerization in the folding and stability of these proteoglycans. We used light scattering to show that biglycan is dimeric in solution and solved the crystal structure of the glycoprotein core of biglycan at 3.40-angstroms resolution. This structure reveals that biglycan dimerizes in the same way as decorin, i.e. by apposition of the concave inner surfaces of the leucine-rich repeat domains. We demonstrate that low concentrations of guanidinium chloride denature biglycan and decorin but that the denaturation is completely reversible following removal of the guanidinium chloride, as assessed by circular dichroism spectroscopy. Furthermore, the rate of refolding is dependent on protein concentration, demonstrating that it is not a unimolecular process. Upon heating, decorin shows a single structural transition at a T(m) of 45-46 degrees C but refolds completely upon cooling to 25 degrees C. This property of decorin enabled us to show both by calorimetry and light scattering that dimer to monomer transition coincided with unfolding and monomer to dimer transition coincided with refolding; thus these processes are inextricably linked. We further conclude that folded monomeric biglycan or decorin cannot exist in solution. This implies novel interrelated functions for the parallel beta sheet faces of these leucine-rich repeat proteoglycans, including dimerization and stabilization of protein folding.

Reviews - 2ft3 mentioned but not cited (2)

  1. From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues. Zappia J, Joiret M, Sanchez C, Lambert C, Geris L, Muller M, Henrotin Y. Biomolecules 10 E80 (2020)
  2. Sequence features, structure, ligand interaction, and diseases in small leucine rich repeat proteoglycans. Matsushima N, Miyashita H, Kretsinger RH. J Cell Commun Signal 15 519-531 (2021)

Articles - 2ft3 mentioned but not cited (9)

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Reviews citing this publication (8)

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  7. Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod-Like and Toll-Like Receptors in Vertebrate Innate Immunity. Matsushima N, Miyashita H, Enkhbayar P, Kretsinger RH. Biomolecules 5 1955-1978 (2015)
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Articles citing this publication (37)

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  13. The crystal structure of the tumor suppressor protein pp32 (Anp32a): structural insights into Anp32 family of proteins. Huyton T, Wolberger C. Protein Sci 16 1308-1315 (2007)
  14. The concave face of decorin mediates reversible dimerization and collagen binding. Islam M, Gor J, Perkins SJ, Ishikawa Y, Bächinger HP, Hohenester E. J Biol Chem 288 35526-35533 (2013)
  15. Proteoglycan and collagen expression during human air conducting system development. Godoy-Guzmán C, San Martin S, Pereda J. Eur J Histochem 56 e29 (2012)
  16. Crystal structure and role of glycans and dimerization in folding of neuronal leucine-rich repeat protein AMIGO-1. Kajander T, Kuja-Panula J, Rauvala H, Goldman A. J Mol Biol 413 1001-1015 (2011)
  17. Structural and functional analysis of two small leucine-rich repeat proteoglycans, fibromodulin and chondroadherin. Paracuellos P, Kalamajski S, Bonna A, Bihan D, Farndale RW, Hohenester E. Matrix Biol 63 106-116 (2017)
  18. ADAMTS-4 and biglycan are expressed at high levels and co-localize to podosomes during endothelial cell tubulogenesis in vitro. Obika M, Vernon RB, Gooden MD, Braun KR, Chan CK, Wight TN. J Histochem Cytochem 62 34-49 (2014)
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