"Structural Biology and Biosynthesis of Collagens"
Extracellular matrix proteins are often composed of multiple domains (regions) with different functions. The 'triple helix' is a structure used in collagens to provide a scaffold for tissues; it forms by polymerization of these extended molecules. The triple helical structure and the stability of such molecules is studied in this project by biophysical-chemical methods.
The biosynthesis of collagens is a complex process that involves alterations of the molecules after their initial synthesis. Enzymes termed peptidyl-prolyl cis-trans isomerases and molecular chaperones that cloak the newly produced molecules influence the folding of the collagen triple helix. Studies on the structure and function of these and related proteins are ongoing.
Other domains found in extracellular matrix proteins include a-helical coiled-coil domains that are often used to pull protein chains into proper configurations. A protein called cartilage matrix protein (CMP) uses this domain to form trimers (molecules composed of three chains) and another termed cartilage oligomeric matrix protein (COMP) forms pentameric (five-chain molecules). A single amino acid substitution in the coiled-coil region of CMP results in the formation of four rather than three chain molecules. Studies on the structure and function of a special domain in COMP are in progress. Mutations in this domain lead to pseudoachondroplasia. In this dwarfing disorder the mutant COMP and type IX collagen are retained inside the cell, leading to a defective cartilage matrix.