title: Crystallization chaperone strategies for membrane proteins.
abstract: From G protein-coupled receptors to ion channels, membrane proteins represent over half of known drug targets. Yet, structure-based drug discovery is hampered by the dearth of available three-dimensional models for this large category of proteins. Other than efforts to improve membrane protein expression and stability, current strategies to improve the ability of membrane proteins to crystallize involve examining many orthologs and DNA constructs, testing the effects of different detergents for purification and crystallization, creating a lipidic environment during crystallization, and cocrystallizing with covalent or non-covalent soluble protein chaperones with an intrinsic high propensity to crystallize. In this review, we focus on this last category, highlighting successes of crystallization chaperones in membrane protein structure determination and recent developments in crystal chaperone engineering, including molecular display to enhance chaperone crystallizability, and end with a novel generic approach in development to target any membrane protein of interest.
authors.affiliation: School of Chemistry and Biochemistry, Institute for Bioscience and Bioengineering, Georgia Institute of Technology, 901 Atlantic Drive NW, Atlanta, GA 30332, USA. raquel.lieberman@chemistry.gatech.edu
authors.forename: Raquel L
authors.initials: RL
authors.lastname: Lieberman
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Culver
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Entzminger
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Pai
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Maynard
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D003902:Detergents / Q000737:chemistry; D006801:Humans; D006825:Hybridomas; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D003902:Detergents; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins