title: Nanobody stabilization of G protein-coupled receptor conformational states.
abstract: Remarkable progress has been made in the field of G protein-coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology. Camelid single chain antibody fragments (nanobodies) show promise for stabilizing active GPCR conformations and as chaperones for crystallogenesis.
authors.affiliation: Department of Molecular and Cellular Interactions, Vlaams Instituut voor Biotechnologie & Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. Jan.Steyaert@vib-vub.be
authors.forename: Jan
authors.initials: J
authors.lastname: Steyaert
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kobilka
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D011487:Protein Conformation; D055550:Protein Stability; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000378:metabolism*
chemical_list: D007128:Immunoglobulin Fragments; D043562:Receptors, G-Protein-Coupled; D057127:Single-Chain Antibodies