2.3 Å Resolution Cryo-EM Structure of Human p97 and Mechanism of Allosteric Inhibition The protein p97 is an AAA adenosine triphosphatase (ATPase) that uses energy from ATP hydrolysis to regulate substrates involved in intracellular protein quality control. Its role in this central process makes it a target for cancer chemotherapy. We used cryo-electron microscopy to determine high-resolution structures for…
Cryo-electron Microscopy Structures of Chimeric Hemagglutinin Displayed on a Universal Influenza Vaccine Candidate Chimeric hemagglutinin proteins are set to undergo human clinical trials as a universal influenza vaccine candidate, yet no structural information for these proteins is available. Using cryo-electron tomography, we report the first three-dimensional (3D) visualization of chimeric hemagglutinin proteins displayed on the surface of the influenza…
Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating Magnesium ions (Mg2+) play essential roles in all living organisms. Bacteria and other prokaryotes rely upon the Mg2+-dependent channel CorA, which is composed of five identical subunits (A-E), to obtain these ions from their surroundings. Studies of CorA showed that, in contrast to most ligand-gated ion channels,…
2.2 Å Resolution Cryo-EM Structure of β-galactosidase in Complex with a Cell-permeant Inhibitor Recent advances in cryo–electron microscopy allow structures of large macromolecules to be determined at near-atomic resolution. So far, though, resolutions approaching 2 Å, where features key to drug design are revealed, remain the territory of x-ray crystallography. Bartesaghi et al. achieved a resolution of 2.2 Å for a…
Structural Mechanism of Glutamate Receptor Activation and Desensitization Understanding the structural basis of the transition from closed to active and desensitized conformations is central to deciphering the function of ionotropic glutamate receptors NMDA receptors, AMPA receptors, delta receptors, and kainate receptors as mediators of excitatory synaptic transmission in the central nervous system. Ligand binding at the receptor's extracellular surface…
Structure of β-galactosidase at 3.2-Å Resolution Obtained by Cryo-Electron Microscopy The vast majority of high-resolution structures obtained using cryo-EM have been typically restricted to large, well-ordered entities such as helical or icosahedral assemblies or two-dimensional crystals. We show here that emerging methods in single-particle cryo-EM now allow structure determination at near-atomic resolution, even for much smaller protein complexes with…
