Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self-interactions in microfibril assembly

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. Structured summary of protein interaction: rFBN1-N binds to rFBN1-C by solid phase assay (View interaction) rFBN1-N binds to rFBN2-C by solid phase assay (View interaction) rFBN2-N binds to rFBN1-C by solid phase assay (View interaction) rFBN2-N binds to rFBN2-C by solid phase assay (View interaction) Fibronectin binds to rFBN2-C by solid phase assay (View interaction) Fibronectin binds to rFBN2-N by solid phase assay (View interaction) Fibronectin binds to rFBN1-N by solid phase assay (View interaction) Fibronectin binds to rFBN1-C by solid phase assay (View interaction) Fibronectin binds to rFBN3-C by solid phase assay (View interaction) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.