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Sharpe Lab


Structure and assembly of membrane-active proteins by solid-state NMR

Integral membrane proteins comprise at least 30 per cent of the proteins encoded in the genomes sequenced to date, and it is estimated that over 80 per cent of potential drug targets are membrane proteins. However, the details of membrane protein structure and function remain elusive. Our current research focuses on elucidating the mechanisms through which integral membrane proteins and membrane-active peptides exert their biological effects, with a specific emphasis on several classes of proteins related to human disease. Our goal is to define the structural elements required for native and aberrant protein activity and to determine the physical basis for membrane alteration in each case. This will significantly improve our understanding of protein-membrane interactions, and will hopefully allow us to identify new targets for therapeutic intervention.

The primary method that we use is solid state nuclear magnetic resonance (NMR) spectroscopy. This method has recently emerged as a powerful tool for structural biology, and allows us to obtain high-resolution data on the structure, macromolecular assembly and dynamic behaviour of integral membrane proteins and fibrillar protein aggregates in their native environments. Additional methods currently being used in the lab to probe membrane and protein structure include circular dichroism, fluorescence spectroscopy and electron microscopy.

Protein structure determination by solid state nuclear magnetic resonance