Recombinant fibrous protein production and applications.

摘要

Fibrous proteins are natural polymers with repetitive units that form higher order structures upon supramolecular interactions. These polymers are most frequently built from structural building blocks owing to the unique mechanical properties that stem from the hierarchical alignment of the smaller units. The facile production of tunable recombinant fibrous proteins as alternatives to their natural protein counterparts and their manipulation for different applications will promote the progress of biomedical research. Collagen is the most abundant fibrous protein in all metazoan life and it is found in a variety of tissues in the body, maintaining the structural integrity while interacting with cells and extracellular molecules. This thesis will focus on collagen and its interactions with cell receptors, as well as collagen diseases. The study of the biological consequences of mutations within the integrin binding region of collagen using the bacterial collagen system increases our understanding of collagen interactions. This thesis improves our molecular understanding of the effects such Gly missense mutations have on integrin binding. The results may have relevance for clarifying the molecular basis of to the subset of OI Gly missense mutations that are within or nearby the integrin binding sequence. This application of the bacterial collagen system illustrates the influence of substitutions and exposes novel outcomes for the interplay between collagen mutations and interactions.