Extracellular proteins

Extracellular Matrix Proteins - towards understanding of biological degradation

This topic is of central importance for aging and cancer, and scientifically closely related to the amyloid project above, in the sense that it focuses on protein aggregate/fibril degradation. We will investigate such degradations from a more systems biology level (using MS proteomics and NMR metabonomcis) under different degrading conditions (proteolysis, #-rays, strong oxidants etc) towards atomic resolution structure determination. Our initial focus will be collagen degradation. Collagen is found in all ECM?s, including skin, bones, tendons, and ligaments. In addition, the protein provides structural integrity all internal organs. As a consequence of this wide distribution, collagen represents one of the most abundant proteins known. Collagen normally turns over at a very slow and controlled rate making it susceptible to the accumulation of protein modification. However, during development and various pathological conditions, like arthritis and cancer, the extent of collagen degradation can increase significantly. Because of the triple helical nature collagen is very stable and only specialized proteases are able to degrade the protein. The mechanism used by these collagenases is not understood in details mainly because of the lack of collagen-collagenase structures.