Membrane Proteins ? Introduction

Abstract

Biomembranes are crucial components in the genesis of life and the structuring elements of the organisation of living cells. They preserve the functional integrity of cell organelles and regulate the exchange of solutes and signals between the different functional areas of the cell. Membrane proteins, which constitute about 30% of the entire protein content of the cell, are often very complex and function in many different ways. A large number of today’s drugs are targeted at membrane proteins. In spite of their importance in modern life sciences, the structure and function of membrane proteins are not well understood, and only few membrane proteins have been investigated in detail. For example, among all protein structures deposited in the protein data bank, membrane protein structures represent only a very small fraction. The reasons for our restricted knowledge of membrane protein assembly, structure and function are limited technologies to express membrane proteins in large quantities, only very little insight into the assembly and folding of membrane proteins and insufficient knowledge how to handle membrane proteins in vitro to study their structure and function in a clearly defined environment without inactivating them. These difficulties arise from the hydrophobic nature of membrane proteins, which have to be transferred into aqueous solution to be accessible for spectroscopic and crystallographic studies on their structure and function. The first three articles of this review series therefore address questions of membrane protein expression, assembly and stability. While membrane proteins from bacteria can be successfully overexpressed in Escherichia coli, overexpression of eukaryotic membrane proteins is more difficult. Eukaryotic membrane proteins, for example Gprotein coupled receptors, which are important for transmembrane signal transduction, often serve as drug targets. The first review article by Alain Milon and co-authors presents currently employed expression systems for this important family among the a-helix-bundle transmembrane proteins. The second review reports on the assembly of membrane proteins of the b-barrel type, which represent one CMLS, Cell. Mol. Life Sci. 60 (2003) 1527–1528 1420-682X/03/081527-2 DOI 10.1007/s00018-003-3167-8 © Birkhauser Verlag, Basel, 2003 CMLS Cellular and Molecular Life Sciences