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Using the site-specific incorporation of isotopically labeled glutamines and NMR, Elena-Real et al. identified helical stability of pathogenic huntingtin exon 1 as a key feature defining the aggregation propensity that triggers Huntington’s disease.
The authors develop an EM-based method to directly visualize R-loops. Applying this method to transcription-replication conflicts in human and bacterial cells, they show that DNA:RNA hybrids accumulate primarily behind replication forks, and are linked to fork slowing and fork reversal.
Recent studies offer new insight on the mechanisms of IP6-mediated HIV-1 capsid assembly. The immature Gag lattice enables enrichment of IP6 into virions, aiding capsid maturation. Structures of capsid protein (CA) assemblies reveal motifs serving as switches modulating the conformations of CA pentamers/hexamers and affect co-factor accessibility.
Park and colleagues found that LARP1 protects mRNA by forming a complex with PABP on short poly(A) tails of ~30–60 nt and thereby serving as a barricade against deadenylases.
Sperm flagella of highly divergent eukaryotic species share an architectural plan. Despite their ostensible ultrastructural similarities, mammalian sperm flagella beat with an asymmetric waveform, in contrast to the symmetrical beats of other eukaryotic flagella. Structural findings elucidate the molecular basis for this evolutionary divergence.
The authors employ cryogenic electron microscopy and kinetic analysis to characterize the discrete steps of how the Dis3L2 3′–5′ exoribonuclease recognizes and degrades structured RNA targets.
By using nuclear pore complex mimics, the authors demonstrate that the cytoplasm-facing Nup358 provides a dock for the HIV-1 capsid, and the nucleoplasm-facing Nup153 positions the capsid for NPC entry. Nup358 and Nup153 thus create an affinity gradient which regulates capsid penetration, whereas Nup62 constitutes a final NPC gatekeeper against HIV-1 capsid entry.
AlphaFold2 has already changed structural biology, but its true power may lie in how it changes the way we think about cells and organisms. Two studies broadly assess its utility and limitations in providing structural models to shed light in areas such as mutations, protein–protein interactions, and phosphorylation.
M. pneumoniae, a model organism for a minimal cell, has a dedicated protein, namely P116, to specifically extract essential lipids. The structure of P116 has a previously unseen fold, resembling a left-handed baseball glove forming a huge hydrophobic cavity.
Polyketide synthase 13 from mycobacteria was purified endogenously ‘in action’ with wild-type substrates bound. Structures by cryo-EM define multiple states of acyl carrier proteins in the final step of mycolic acid synthesis by a key drug target.
The authors use single-particle cryo-EM to analyze the fullerene cone structure of the HIV-1 capsid. They identify a hexamer/pentamer switch that allows for cone assembly and modulates the ligand-binding properties of the capsid.
Cryo-EM of human PRPS1 shows the nucleotide-synthesizing enzyme assembling into filaments that accommodate active and inhibited conformations. Engineered and disease mutations reveal that filament assembly stabilizes allosteric sites, enhancing catalytic activity.
Tan et al. found that topoisomerase-independent DNA nicking is required for most, if not all, signal-induced acute enhancer activation programs, nucleating formation of a Ku70–HP1γ–Med26 complex required to facilitate transcriptional activation.
Postel et al. have determined a multidomain structure of GR in complex with ligand, DNA and a co-regulator peptide that demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore.
Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.