title: Protein engineering methods applied to membrane protein targets.
abstract: Genes encoding membrane proteins have been estimated to comprise as much as 30% of the human genome. Among these membrane, proteins are a large number of signaling receptors, transporters, ion channels and enzymes that are vital to cellular regulation, metabolism and homeostasis. While many membrane proteins are considered high-priority targets for drug design, there is a dearth of structural and biochemical information on them. This lack of information stems from the inherent insolubility and instability of transmembrane domains, which prevents easy obtainment of high-resolution crystals to specifically study structure-function relationships. In part, this lack of structures has greatly impeded our understanding in the field of membrane proteins. One method that can be used to enhance our understanding is directed evolution, a molecular biology method that mimics natural selection to engineer proteins that have specific phenotypes. It is a powerful technique that has considerable success with globular proteins, notably the engineering of protein therapeutics. With respect to transmembrane protein targets, this tool may be underutilized. Another powerful tool to investigate membrane protein structure-function relationships is computational modeling. This review will discuss these protein engineering methods and their tremendous potential in the study of membrane proteins.
authors.affiliation: Department of Chemistry and Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO 80309, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Lluis
authors.forename: J I
authors.initials: JI
authors.lastname: Godfroy
authors.forename: H
authors.initials: H
authors.lastname: Yin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D003460:Crystallization; D019020:Directed Molecular Evolution; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D011994:Recombinant Proteins