Of the known 28 types of collagen, heterotrimeric fibrillar and non-fibrillar collagens constitute a special class that bind to a diverse group of cell surface transmembrane receptors and extracellular matrix proteins through specialized amino acid epitopes and regulate immune response, hemostasis and cell signaling. In vitro binding of short collagen mimetic peptides containing the recognition epitopes of these proteins has provided valuable insights into the mechanism of their binding and function, but with a caveat that nearly all triple helices were homotrimeric. We recently showed that salt-bridge interactions in collagen are geometrically constrained and can be used as keystone interactions to design AAB heterotrimers. Here, we show the successful design of composition and register specific AAB-type heterotrimers containing the epitope required for binding to integrin a1�1. Using this designed heterotrimer we have also investigated collagen-protein binding via Nuclear Magnetic Resonance Spectroscopy and solid phase binding assays. This work will help to elucidate the unique collagen binding interactions as presented by heterotrimeric collagens.

Design and testing of a heterotrimeric collagen presenting an integrin binding site

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.