Open AccessStabilization of Membrane Proteins: the Case of G‐Protein‐Coupled Receptors
Author(s) -
ReyesAlcaraz A.,
Tzanov T.,
Garriga P.
Publication year - 2008
Publication title -
engineering in life sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.547
H-Index - 57
eISSN - 1618-2863
pISSN - 1618-0240
DOI - 10.1002/elsc.200700059
Subject(s) - receptor , g protein coupled receptor , membrane protein , biochemistry , signal transduction , integral membrane protein , g protein , cell surface receptor , rhodopsin like receptors , biology , lipid bilayer , chemistry , biophysics , microbiology and biotechnology , membrane , metabotropic receptor , agonist
G‐protein‐coupled receptors are integral membrane proteins which constitute the largest family of signal transduction molecules participating in the majority of normal physiological processes. G‐protein‐coupled receptors are responsible for the control of enzyme activity, ion channels and vesicle transport, and they respond to a wide variety of stimuli, like signals involved in sensory systems such as vision, taste and olfaction, but also to a diverse set of chemical signals such as lipids, hormones, neurotransmitters, amino acids, nucleotides, peptides and proteins. This family of receptors is being widely studied because of its potential use as pharmacological targets in drug development, and recently also for its potential use in the development of novel biosensors. G‐protein‐coupled receptors are specifically designed to fold and function in a lipid bilayer environment, where these membrane proteins are remarkably stable and achieve their optimal performance. The currently used technology for the purification of G‐protein‐coupled receptors consists in their extraction from the cell membrane and solubilization into detergent micelles. A common drawback of this strategy is that G‐protein‐coupled receptors solubilized in typical detergents show rather poor conformational stability, which may result in relatively rapid inactivation. The poor stability of detergent‐solubilized samples renders many membrane proteins biochemically intractable. This precludes the determination of a high‐resolution structure and imposes severe limitations for the development of applications. Thus, the enhancement of the stability of G‐protein‐coupled receptors is a major issue in order to facilitate structural determination and to unravel their potential in biotechnological applications. This work provides a brief overview of some current advances in the experimental methods for stabilizing G‐protein‐coupled receptors that can also be extended to other types of membrane proteins.