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The cryo-EM structure of the bovine rod CNG channel, isolated from retina, sheds light onto the structural basis for the subunit stoichiometry and reveals an additional gate within the ion conduction pathway contributed by the CNGB1 subunit.
A cryo-EM structure of the human cone photoreceptor CNG channel reveals an odd subunit stoichiometry and unique structural features conferred by a distinct subunit, providing a framework to study cone CNG channel physiology and channelopathies.
A cryo-EM structure of the Dbf4-dependent kinase (DDK) in the act of phosphorylating an Mcm2-7 helicase complex reveals how DDK selectively targets DNA-loaded MCM double hexamers to trigger replication origin activation. Checkpoint kinase Rad53 blocks origin firing by impairing double hexamer engagement by DDK.
Cryo-EM structures of the cytosolic metazoan GET complex, which targets nascent tail-anchored membrane proteins to the endoplasmic reticulum, reveal interactions that coordinate client transfer between two protein chaperones.
Here the authors structurally investigate elongating human RNA polymerase I at 2.7 Å using cryo-electron microscopy, as well as an RNA polymerase I open complex at 3.3 Å and bound to initiation factor RRN3 at 3.2 Å.
Genetic and genomic analyses show that S. cerevisiae DNA polymerase δ extrinsically proofreads for errors by polymerase ε and itself, and demonstrate that the symmetry of replication fidelity is achieved via coordinated efforts of intrinsic and extrinsic proofreading and DNA mismatch repair.
Cryo-EM and three-dimensional variability analyses reveal the structure of the autoinhibited 640-kDa NF1 dimer, providing a long-sought-after molecular explanation for the extreme sensitivity of the NF1 gene to loss-of function mutation in disease.
The discovery that mRNA degradation and deadenylation are uncoupled during meiosis in budding yeast provides a unique context to examine the regulation of each process individually, and reveals that transcript length is a determinant of deadenylation rates across eukaryotes.
Structures of antifungal AmB ‘sponges’ are illuminated by high-resolution SSNMR. These AmB assemblies consist of asymmetric head-to-tail homodimers staggered in a clathrate-like lattice with large void volumes similar to the size of sterols.
MacroH2A histone variants originated before the split of fungi and animals. ADP-ribose binding is an ancestral feature of their macrodomains and is linked to the compartmental regulation of NAD metabolism. This function was selected for during the evolution of metazoans.
How p97 processes diverse clients has remained controversial. van den Boom, Kueck and colleagues now demonstrate that p97 recognizes an internal segment of the PP1 partner I3 and then threads an I3 peptide loop through the channel in p97 to strip I3 off PP1.
The cryo-EM structure of the human SAGA coactivator complex reveals high-resolution details of the core and TRRAP modules, providing insights on a metazoan-specific architecture and the structural basis for incorporation of the splicing module in mammalian cells.
This study reveals the structural basis for the coupling specificity of one G-protein-coupled receptor, the β1-adrenergic receptor, to two different families of G proteins. Although the receptor adopts the same conformation, the G proteins have different interaction modes dictated by the overall structure.
Comparative analysis of inactive/active-state structures reveals molecular mechanistic maps of activation of the major GPCR classes. The findings and new approaches lay the foundation for targeted receptor-function studies and drugs with desired modalities.
NMR visualization of phase-separated FUS and RNA polymerase II domains in models of transcriptional condensates show that a much wider array of residue types and interaction modes stabilize phases than previously proposed.
Dynamic changes in 2′-O-methylation of rRNA in human cells lead to ribosome heterogeneity and result in altered translation of select mRNAs, correlating with changes in cellular phenotypes.
Biochemical, biophysical and structural analysis reveals how the scaffolding protein CcmM recruits the enzymes Rubisco and carbonic anhydrase into a condensate for encapsulation into carboxysomes—microcompartments in cyanobacteria that serve to optimize CO2 assimilation.
Fluorescence imaging and fluorescence recovery after photobleaching assays reveal that the mitochondrial nucleoid forms a suborganelle via liquid–liquid phase separation interactions between mitochondrial DNA and the mitochondrial transcriptional machinery.
A structural model of a K-Ras nanocluster that promotes the stability and accessibility of active K-Ras and creates composite interfaces that facilitate Raf binding provides a framework to unravel MAPK signaling.
Cryo-EM and X-ray crystal structures reveal the architecture of the human Xkr8–Basigin complex, providing insights into the molecular mechanism of phospholipid scrambling.