Tailoring yeast for human membrane protein structural biology; humanizing yeast membrane lipid composition

Controlled exchange of matter and information between a cell’s interior and exterior is performed exclusively by chemically selective membrane spanning proteins. Understanding membrane protein structure is therefore vital for comprehending human physiology. However, essentially all human membrane proteins cannot be purified from native tissue and are challenging to produce and purify. We have successfully developed a yeast expression platform for human membrane protein production resulting in a number of high resolution membrane protein structures. However, the lipid environment experienced by a human membrane protein produced in yeast deviates significantly from that present in the native human cell. This includes phospholipid fatty acid chain length, degree of fatty acid unsaturation and steroid composition. To deposit recombinant human membrane proteins in a more native-like environment we will engineer our yeast expression system to make membranes resembling those found in humans.