@article {65635,
	title = {Structure of human GABA receptor in an inactive state.},
	journal = {Nature},
	volume = {584},
	year = {2020},
	month = {2020 Aug 01},
	pages = {304-9},
	abstract = {<p>The human GABA receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction. A unique GPCR that is known to require heterodimerization for function, the GABA receptor has two subunits, GABA and GABA, that are structurally homologous but perform distinct and complementary functions. GABA recognizes orthosteric ligands, while GABA couples with G proteins. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail. Although the VFT heterodimer structure has been resolved, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABA receptor at atomic resolution, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique {\textquoteright}intersubunit latch{\textquoteright} within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.</p>
},
	issn = {1476-4687},
	doi = {10.1038/s41586-020-2452-0},
	author = {Park, Jinseo and Fu, Ziao and Frangaj, Aurel and Liu, Jonathan and Mosyak, Lidia and Shen, Tong and Slavkovich, Vesna N and Ray, Kimberly M and Taura, Jaume and Cao, Baohua and Geng, Yong and Zuo, Hao and Kou, Yongjun and Grassucci, Robert and Chen, Shaoxia and Liu, Zheng and Lin, Xin and Williams, Justin P and Rice, William J and Eng, Edward T and Huang, Rick K and Soni, Rajesh K and Kloss, Brian and Yu, Zhiheng and Javitch, Jonathan A and Hendrickson, Wayne A and Slesinger, Paul A and Quick, Matthias and Graziano, Joseph and Yu, Hongtao and Fiehn, Oliver and Clarke, Oliver B and Frank, Joachim and Fan, Qing R}
}
@article {6332,
	title = {Tilt-pair analysis of images from a range of different specimens in single-particle electron cryomicroscopy.},
	journal = {Journal of Molecular Biology},
	volume = {413},
	year = {2011},
	month = {2011 Nov 11},
	pages = {1028-46},
	abstract = {<p>The comparison of a pair of electron microscope images recorded at different specimen tilt angles provides a powerful approach for evaluating the quality of images, image-processing procedures, or three-dimensional structures. Here, we analyze tilt-pair images recorded from a range of specimens with different symmetries and molecular masses and show how the analysis can produce valuable information not easily obtained otherwise. We show that the accuracy of orientation determination of individual single particles depends on molecular mass, as expected theoretically since the information in each particle image increases with molecular mass. The angular uncertainty is less than 1{\textdegree} for particles of high molecular mass (\&nbsp;50 MDa), several degrees for particles in the range 1-5 MDa, and tens of degrees for particles below 1 MDa. Orientational uncertainty may be the major contributor to the effective temperature factor (B-factor) describing contrast loss and therefore the maximum resolution of a structure determination. We also made two unexpected observations. Single particles that are known to be flexible showed a wider spread in orientation accuracy, and the orientations of the largest particles examined changed by several degrees during typical low-dose exposures. Smaller particles presumably also reorient during the exposure; hence, specimen movement is a second major factor that limits resolution. Tilt pairs thus enable assessment of orientation accuracy, map quality, specimen motion, and conformational heterogeneity. A convincing tilt-pair parameter plot, where 60\% of the particles show a single cluster around the expected tilt axis and tilt angle, provides confidence in a structure determined using electron cryomicroscopy.</p>
},
	keywords = {Adenosine Triphosphatases, Animals, beta-Galactosidase, Cattle, Computer-Assisted, Cryoelectron Microscopy, Image Processing, Rotavirus, Virion, Yeasts},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2011.09.008},
	author = {Henderson, Richard and Chen, Shaoxia and Chen, James Z and Grigorieff, Nikolaus and Passmore, Lori A and Ciccarelli, Luciano and Rubinstein, John L and Crowther, R Anthony and Stewart, Phoebe L and Rosenthal, Peter B}
}
