Search

Structures of radial spokes and associated complexes important for ciliary motility

Journal Article

In motile cilia, a mechanoregulatory network is responsible for converting the action of thousands of dynein motors bound to doublet microtubules into a single propulsive waveform. Here, we use two complementary cryo-EM strategies to determine structures...

A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent

Journal Article

Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves as the cellular receptor for severe acute respiratory...

Cryo-EM structure of an activated GPCR–G protein complex in lipid nanodiscs

Journal Article

G-protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR–G protein complexes, few are in a lipid...

Structural impact on SARS-CoV-2 spike protein by D614G substitution

Journal Article

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms...

DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation

Journal Article

Nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 1 (NLRP1) is an inflammasome sensor that mediates the activation of caspase-1 to induce cytokine maturation and pyroptosis1–4. Gain-of-function mutations of NLRP1 cause...

Structure of a microtubule-bound axonemal dynein

Journal Article

Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins...

Functional refolding of the penetration protein on a non-enveloped virus

Journal Article

A non-enveloped virus requires a membrane lesion to deliver its genome into a target cell1. For rotaviruses, membrane perforation is a principal function of the viral outer-layer protein, VP42,3. Here we describe the use of electron cryomicroscopy to...

Multiple domain interfaces mediate SARM1 autoinhibition

Journal Article

Axon degeneration is an active program of subcellular self-destruction that drives pathology in the injured and diseased nervous system. SARM1 is an inducible NAD+ hydrolase and the central executioner of axon loss. In healthy axons, the SARM1 NADase is...

Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis

Journal Article

The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an $\alpha$7$\beta$7$\beta$7$\alpha$7 configuration. CP biogenesis proceeds through an ordered multistep pathway...

STING cyclic dinucleotide sensing originated in bacteria

Journal Article

Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides that are released during bacterial infection and in endogenous cyclic GMP–AMP signalling during viral infection and anti-tumour immunity1–5. STING...

CBASS Immunity Uses CARF-Related Effectors to Sense 3′–5′- and 2′–5′-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection

Journal Article

Summary cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated...

Gasdermin D pore structure reveals preferential release of mature interleukin-1

Journal Article

As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as...