![]() The importance of these interactions is seen in the development of diseases, such as Marfan syndrome, in which mutations in fibrillin-1 lead to a loss of structural integrity in the extracellular matrix and perturbations in transforming growth factor β (TGF-β) signaling ( Ramirez and Dietz, 2007).Īlthough it has been known for several years that fibrillin is the main structural component of the microfibrils ( Sakai et al., 1986), the precise organization of individual fibrillin molecules within the microfibrils is still controversial. They also interact with a variety of other cell-matrix components. In addition to these biomechanical functions, the microfibrils are also involved in the regulation of growth factors through the interactions of their major component, the fibrillins, with the latent transforming growth factor-β binding proteins (LTBPs) and bone morphogenetic proteins ( Chaudhry et al., 2007 Gregory et al., 2005 Isogai et al., 2003 Neptune et al., 2003 Sengle et al., 2008). In nonelastic tissues, such as the ciliary zonule of the eye and at basement membranes, they have an anchoring function and provide tissues with tensile strength ( Kumaratilake et al., 1989). During elastogenesis, they provide a scaffold for the deposition of tropoelastin and form the periphery of the mature elastic fiber. The 10–12 nm fibrillin microfibrils of the extracellular matrix play important roles in both elastic and nonelastic tissues. 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. Pairwise interactions with neighboring cbEGF domains demonstrate extensive interfaces, with the hyb2-cbEGF10 interface dependent on Ca 2+ binding. The hybrid domain fold is similar, but not identical, to the TB domain fold seen in previous fibrillin-1 and LTBP-1 fragments. Here we present the crystal structure of a fibrillin-1 cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 Å resolution. Fibrillins are the major components of the extracellular 10–12 nm diameter microfibrils, which mediate a variety of cell-matrix interactions. The fibrillins and latent transforming growth factor-β 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 β-binding protein-like (TB) and hybrid (hyb) domains. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |