Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins.

Journal article

The fibrillins and latent transforming growth factor-beta binding proteins (LTBPs) form a superfamily of structurally-related proteins consisting of calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with 8-cysteine-containing transforming growth factor beta-binding protein-like (TB) and hybrid (hyb) domains. Fibrillins are the major components of the extracellular 10-12 nm diameter microfibrils, which mediate a variety of cell-matrix interactions. Here we present the crystal structure of a fibrillin-1 cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 A resolution. The hybrid domain fold is similar, but not identical, to the TB domain fold seen in previous fibrillin-1 and LTBP-1 fragments. Pairwise interactions with neighboring cbEGF domains demonstrate extensive interfaces, with the hyb2-cbEGF10 interface dependent on Ca(2+) binding. These observations provide accurate constraints for models of fibrillin organization within the 10-12 nm microfibrils and provide further molecular insights into how Ca(2+) binding influences the intermolecular interactions and biomechanical properties of fibrillin-1.

Authors: Jensen, SA; Iqbal, S; Lowe, E; Redfield, C; Handford, P

• Publication status: Published
• Journal: Structure (London, England : 1993)
• Volume: 17
• Issue: 5
• Pages: 759-768
• Publication date: 2009-05-01
• DOI: 10.1016/j.str.2009.03.014
• EISSN: 1878-4186
• ISSN: 0969-2126
• Language: English
• Keywords: Calcium; Amino Acid Sequence; Molecular Sequence Data; Models, Molecular; Latent TGF-beta Binding Proteins; Calcium-Binding Proteins; Protein Conformation; Structure-Activity Relationship; Microfilament Proteins; Endothelial Growth Factors; Disulfides; Protein Structure, Tertiary; Binding Sites