Interactions of Fibrillin-1 with Heparin/Heparan Sulfate, Implications for Microfibrillar Assembly

Kerstin Tiedemann, Boris Bätge, Peter K. Müller, Dieter P. Reinhardt*

*Corresponding author for this work
119 Citations (Scopus)

Abstract

Fibrillin-1 is a major constituent of the 10-12 nm extracellular microfibrils. Here we identify, characterize, and localize heparin/heparan sulfate-binding sites in fibrillin-1 and report on the role of such glycosaminoglycans in the assembly of fibrillin-1. By using different binding assays, we localize two calcium-independent heparin-binding sites to the N-terminal (Arg45-Thr450) and C-terminal (Asp 1528-Arg2731) domains of fibrillin-1. A calcium-dependent-binding site was localized to the central (Asp 1028-Thr1486) region of fibrillin-1. Heparin binding to these sites can be inhibited by a highly sulfated and iduronated form of heparan sulfate but not by chondroitin 4-sulfate, chondroitin 6-sulfate, and dermatan sulfate, demonstrating that the heparin binding regions represent binding domains for heparan sulfate. When heparin or heparan sulfate was added to cultures of skin fibroblasts, the assembly of fibrillin-1 into a microfibrillar network was significantly reduced. Western blot analysis demonstrated that this effect was not due to a reduced amount of fibrillin-1 secreted into the culture medium. Inhibition of the attachment of glycosaminoglycans to core proteins of proteoglycans by β-D-xylosides resulted in a significant reduction of the fibrillin-1 network. These studies suggest that binding of fibrillin-1 to proteoglycan-associated heparan sulfate chains is an important step in the assembly of microfibrils.

Original languageEnglish
JournalJournal of Biological Chemistry
Volume276
Issue number38
Pages (from-to)36035-36042
Number of pages8
ISSN0021-9258
DOIs
Publication statusPublished - 21.09.2001

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Fingerprint

Dive into the research topics of 'Interactions of Fibrillin-1 with Heparin/Heparan Sulfate, Implications for Microfibrillar Assembly'. Together they form a unique fingerprint.

Cite this