A Role for Lipid-Protein Interaction in Intergral Membrane Protein Function

Abstract

The fukutins are a family of eukaryotic membrane proteins whose mis-localisation within the cell has been shown to be associated with the onset of Fukuyama muscular dystrophy. The interaction between the N-terminal transmembrane domain fukutin with the atypical lipid bilayer of the Golgi apparatus has been postulated to play a crucial role in the retention of the protein there.To investigate the nature of these interactions we have developed a bacterial expression system for isolating the N-terminal transmembrane domain of Fukutin-I. We have characterised this hydrophobic peptide using molecular biology techniques, mass spectrometry, circular dichroism and nuclear magnetic resonance studies.Currently, we are using solid state NMR and fluorescence studies to analyse how the oligomeric state, lateral segregation and structure of fukutin reconstituted into artificial bilayers varies as a function of varying lipid compositions. These studies will provide further insight into the role of lipid-protein interactions in membrane protein structure and assembly, segregation into lipid rafts and the role these properties may play in protein trafficking.