Structural Study of Heme Proteins by Electron Microscopy of 2-Dimensional Crystals

Characterization of membrane proteins has always lagged behind that of soluble proteins, because most techniques of protein purification and structural study depend upon having a water-soluble preparation. The development of myriad classes of detergents over the past decades has greatly facilitated the purification of integral membrane proteins and many of the techniques of structural characterization. Direct measurement of the 3-dimensional (3D) structures of integral membrane proteins has proceeded more slowly, but significant progress was made in the past 10 to 15 years, and the atomic structures of a number of membrane proteins are now known. Although X-ray crystallography and 2-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy have been used to elucidate the structures of thousands of soluble proteins, their utility in the structural study of membrane proteins has been limited by the difficulty of growing 3D crystals in the case of X-ray techniques or by the large size of protein-detergent micelles in the case of NMR spectroscopy.