• Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
    • Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
    • Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
    • ,
    •   Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to…
  • Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs
  • Structure of rhodopsin bound to an inhibitory G protein
    • Structure of rhodopsin bound to an inhibitory G protein
    • Structure of rhodopsin bound to an inhibitory G protein
    • ,
    •   Cryo-EM structure of human rhodopsin bound to an inhibitory G protein For the first time, scientists have visualized the interaction between two critical components of the body’s vast cellular communication network, a discovery that could lead to more effective medications with fewer side effects for conditions ranging from migraine to cancer. The near-atomic resolution images obtained, show a G-protein coupled…
  • Atomic Resolution Structure of B-galactosidase
    • Atomic Resolution Structure of B-galactosidase
    • Atomic Resolution Structure of B-galactosidase
    • ,
    •   Atomic Resolution Cryo-EM Structure of B-galactosidase We report methods to account for radiation damage and local changes in defocus and image drift, enabling visualization of atomic resolution features in a cryo-EM density map of inhibitor-bound -galactosidase, and derivation of atom-specific measures of local flexibility of the bound inhibitor using constrained molecular dynamics simulations. Structure, 26(6), p. 848-85, 2018.
  • DNA Targeting by a CRISPR-Cas Complex
    • DNA Targeting by a CRISPR-Cas Complex
    • DNA Targeting by a CRISPR-Cas Complex
    • ,
    •   Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex Electron-microscopy images reveal how a CRISPR system marks specific DNA sequences for destruction. Microbes use CRISPR as a defense system to fend off viruses and other invaders, and geneticists have harnessed it to alter DNA sequences in a process called gene editing. We used cryo-electron microscopy…
  • Proteins Involved in Cancer Cell Metabolism
    • Proteins Involved in Cancer Cell Metabolism
    • Proteins Involved in Cancer Cell Metabolism
    • ,
    •   Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery Using cryo-EM we were able to capture images of glutamate dehydrogenase (GDH), an enzyme found in cells, at a resolution of 1.8 angstroms, a level of detail at which the structure of the central parts of the enzyme could be visualized in atomic detail. We also imaged two small proteins in…
  • Human p97 and Mechanism of Allosteric Inhibition
    • Human p97 and Mechanism of Allosteric Inhibition
    • Human p97 and Mechanism of Allosteric Inhibition
    • ,
    •   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…
  • Mapping Small Ligands on Dynamic Metabolic Enzymes
  • Cryo-EM Analysis of Human P-glycoprotein
  • Structures of Chimeric Hemagglutinin on Influenza Virus
    • Structures of Chimeric Hemagglutinin on Influenza Virus
    • Structures of Chimeric Hemagglutinin on Influenza Virus
    • ,
    •   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…
  • Structure of Magnesium Channel CorA
    • Structure of Magnesium Channel CorA
    • Structure of Magnesium Channel CorA
    • ,
    •   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,…
  • β-galactosidase Bound to Cell-Permeant Inhibitor
    • β-galactosidase Bound to Cell-Permeant Inhibitor
    • β-galactosidase Bound to Cell-Permeant Inhibitor
    • ,
    •   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…
  • Structure of Ebola Glycoprotein Mucin-like Domain
  • Three-state Solution for Glutamate Receptor Structure
    • Three-state Solution for Glutamate Receptor Structure
    • Three-state Solution for Glutamate Receptor Structure
    • ,
    •   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
    • Structure of β-galactosidase at 3.2-Å Resolution
    • Structure of β-galactosidase at 3.2-Å Resolution
    • ,
    •   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…
  • Prefusion Structure of Trimeric HIV-1
    • Prefusion Structure of Trimeric HIV-1
    • Prefusion Structure of Trimeric HIV-1
    • , ,
    •   Prefusion Structure of Trimeric HIV-1 Envelope Glycoprotein Determined by Cryo-Electron Microscopy HIV-1 Env transitions from a closed to an open state upon binding to its cellular receptor. Single-particle cryo-EM analysis now reveals the closed state of the HIV-1 Env trimer at ~6-Å resolution, featuring three gp41 helices at the center of the trimer. These findings indicate that HIV-1 enters…