Biophysical EPR Studies Applied to Membrane Proteins

Membrane proteins are intermediates to the cells and play an essential role in controlling the cell function, ion movement across a cell, and signal transduction within cell membranes. Genes encoding membrane proteins consists of ~30 % of human and E. coli genomes . Mutations in genes and misfolding of membrane proteins are linked to several human dysfunctions, disorders and diseases, e. g., rhodopsin misfolding causes retinitis pigmentosa, and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) can cause a potentially fatal disease in children. More than 50% of membrane proteins are potential drug targets .

Detailed structural and dynamic information is very important to understand the proper functions and regulations of membrane proteins. However structure and dynamic information on membrane proteins is still lagging behind those of soluble proteins. Challenges in studying membrane proteins arise due to the hydrophobic nature of membrane proteins making overexpression,purification, and crystallization more difficult and lacking of suitable solubilizing membrane mimetics. Membrane proteins are incorporated into a lipid bilayer in several different fashions or orientations. The membrane bound helices may be short, long, kinked, or interrupted in the middle of the lipid bilayer. They may cross the membrane at different angles, lie flat on membrane surface or form re-entrant loops.