The structure and assembly of collagen VI using cryo-EM and SAXS

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The extracellular matrix is all the material that is found outside of the cell and it makes up most of the tissues in our bodies. The matrix is composed of an intricate network of proteins which provides support for cells and the framework for tissues. The structure and organisation of most matrix proteins is poorly understood as they are very complicated, and it has proved a major challenge to understand their organisation. However, new approaches are now beginning to reveal important information on their assembly and structural organisation. Collagen VI microfibrils are important components of the extracellular matrix. These microfibrils have widespread distributions throughout the body where they form many linkages between cells and proteins. Mutations in collagen VI are linked to inherited muscular dystrophies, highlighting how important it is to study this molecule. The aims of this project are to investigate the structure and function of collagen VI microfibrils using the technique of cryo-Electron Microscopy. Many low contrast images of frozen hydrated microfibrils will be averaged to produce a 3D structure. Further details will be added by looking at the shape of small fragments of the collagen VI protein and mapping these onto the 3D structure of the microfibril. We will also look at larger assemblies of collagen VI in lattice-like structures, similar to those found in human tissues. The structure produced from these data will increase our understanding of the organisation of these complicated microfibrils.