Heparin/heparan sulfate controls fibrillin‐1, ‐2 and ‐3 self‐interactions in microfibril assembly. Issue 17 (14th July 2014)

• Record Type: Journal Article
• Authors: Sabatier, Laetitia; Djokic, Jelena; Hubmacher, Dirk; Dzafik, Dzaner; Nelea, Valentin; Reinhardt, Dieter P.
• Is Part Of: FEBS letters. Volume 588:Issue 17(2014)
• Page Start: 2890
• Page End: 2897
• Publication Date: 2014-07-14
• Subjects: BSA -- bovine serum albumin -- cbEGF -- calcium-binding epidermal growth factor-like domain -- MAGP-1 -- microfibril-associated glycoprotein-1 -- TB -- transforming growth factor-β binding domain -- TBS -- Tris-buffered saline -- TBST -- TBS/Tween-20 -- Fibrillin -- Assembly -- Microfibrils -- Heparan sulfate -- Extracellular matrix -- Connective tissue -- Fibronectin; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.06.061
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Fibrillins form multifunctional microfibrils in most connective tissues. Deficiencies in fibrillin assembly can result in fibrillinopathies, such as Marfan syndrome. We demonstrate the presence of heparin/heparan sulfate binding sites in fibrillin‐2 and ‐3. Multimerization of all three fibrillins drastically increased the apparent affinity of their interaction with heparin/heparan sulfate. Surprisingly, contrary to other reports heparin/heparan sulfate strongly inhibited homo‐ and heterotypic N‐to‐C‐terminal fibrillin interactions. These data suggest that heparin/heparan sulfate controls the formation of microfibrils at the bead interaction stage. Abstract : Fibrillins assemble into ordered extracellular microfibrils via a complex mechanism. Multimerization of all three fibrillins drastically increased the apparent affinity for heparin/heparan sulfate. Heparin/heparan sulfate strongly inhibited homo‐ and heterotypic N‐to‐C‐terminal fibrillin interactions. Heparin/heparan sulfate controls the formation of microfibrils at the bead interaction stage.