The family of G-protein coupled receptors includes a wide variety of proteins that provide the transmembrane signaling pathway in response to stimuli such as light, oderants, hormones, cytokines, and neuropeptides. Thus members of the family are involved in a great number of important events in the cell's response to its environment, and there is great interest in the pharmaceutical properties of these proteins. All of the receptors are characterized by a structure that includes seven transmembrane alpha helices. To date the only seven-helix protein whose structure is known at high resolution is bacteriorhodopsin (bR), the light-driven proton pump from halobacteria. While there has been some success in modeling structures and properties of some of the other seven- helix proteins based on the bR structure and conserved characteristics of the amino acid sequences of the proteins, it is clear the direct structural information on other members of the receptor family will be necessary before we can fully understand their properties. We propose to develop methods for crystallizing proteins of this family in two dimensions, to produce specimens suitable for study by electron crystallography. We have chosen three proteins to work with that are each well characterized and available in sufficient quantity, purity and activity to be suitable for crystallization trials. These are bovine rhodopsin in complex with arrestin, the yeast mating factor Ste2p, and the human beta-2 adrenergic receptor.
| Zhang, Rui; LaFrance, Benjamin; Nogales, Eva (2018) Separating the effects of nucleotide and EB binding on microtubule structure. Proc Natl Acad Sci U S A 115:E6191-E6200 |
| Nogales, Eva (2018) Cytoskeleton in high resolution. Nat Rev Mol Cell Biol 19:142 |
| Downing, Kenneth H; Glaeser, Robert M (2018) Estimating the effect of finite depth of field in single-particle cryo-EM. Ultramicroscopy 184:94-99 |
| Nogales, Eva (2018) Cryo-EM. Curr Biol 28:R1127-R1128 |
| Sazzed, Salim; Song, Junha; Kovacs, Julio A et al. (2018) Tracing Actin Filament Bundles in Three-Dimensional Electron Tomography Density Maps of Hair Cell Stereocilia. Molecules 23: |
| Kamennaya, Nina A; Zemla, Marcin; Mahoney, Laura et al. (2018) High pCO2-induced exopolysaccharide-rich ballasted aggregates of planktonic cyanobacteria could explain Paleoproterozoic carbon burial. Nat Commun 9:2116 |
| Howes, Stuart C; Geyer, Elisabeth A; LaFrance, Benjamin et al. (2018) Structural and functional differences between porcine brain and budding yeast microtubules. Cell Cycle 17:278-287 |
| Glaeser, Robert M (2018) PROTEINS, INTERFACES, AND CRYO-EM GRIDS. Curr Opin Colloid Interface Sci 34:1-8 |
| Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon et al. (2018) Near-atomic model of microtubule-tau interactions. Science 360:1242-1246 |
| Han, Bong-Gyoon; Watson, Zoe; Cate, Jamie H D et al. (2017) Monolayer-crystal streptavidin support films provide an internal standard of cryo-EM image quality. J Struct Biol 200:307-313 |
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