In meso Approaches to Membrane Protein Crystallization - Molecules: Nucleation, Aggregation and Crystallization - page 260

organisms to hold their breaths longer. In 1958, Kendrew and associates suc-
cessfully determined the structure of myoglobin by high-resolution X-ray
crystallography (Kendrew et al. , 1958). For this discovery, John Kendrew
shared the 1962 Nobel Prize in Chemistry with Max Perutz. Hemoglobin, the
oxygen-carrying pigment found in red blood cells, was one of the first pro-
teins to have its three-dimensional structure resolved by X-ray crystallogra-
phy (by Max Perutz in the early 1960s (Perutz, 1962)).
Currently, the RCSB Data Bank contains over 20 000 structures, but
only about 30 are structures of different membrane proteins (Loll, 2003;
Ruahani et al ., 2002), in spite of the fact that the topic of membranes occu-
pies a central position in cell and molecular biology. It has become clear
in recent years that the study of membranes at the molecular level is of
great importance not only in the deciphering of all cellular processes but
also in the understanding of the alterations leading to abnormal (trans-
formed) cells and the action of drugs.
Membrane proteins are the main functional units of membranes and
represent roughly one third of the proteins encoded in the genome, and yet
70% of drugs have membrane proteins as a target. However, they comprise
only 1% of proteins of known structure.
High-throughput crystallography offers hope of correcting this imbal-
ance. However, for large-scale membrane protein structural biology to
realize its full promise, significant challenges must be overcome. One of
the most substantial of them is the development of reliable methods for
membrane protein crystal growth (Loll, 2003; Ruahani, et al ., 2002).
Usually, to crystallize membrane proteins one first has to solubilize them
with a detergent. However, it is not an easy problem to find a proper
detergent to obtain a stable and functional protein. The difficulty is that
the natural environment of these proteins is a lipid bilayer.
Membrane Protein Crystallization: A Standard
Approach
Detergents are a relatively poor substitute for the lipid bilayer and mem-
brane proteins are often unstable outside the membrane (Michel, 1991).