Volume 30 Issue 3, March 2023

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.

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.

The RNA methyltransferase (MTase) METTL1 catalyzes N⁷-methylguanosine (m⁷G) modification at position 46 in human transfer RNAs (tRNAs). Its dysregulation drives tumorigenesis in many cancer types. Two papers now reveal the structural basis of this tRNA maturation event.

In this Review, the authors provide a comprehensive overview of recent structural studies of the cGAS–STING complex, discussing pertinent functional and mechanistic implications.

The Shigella effector OspC3 is activated by binding of host calmodulin to its ADP-riboxanase domain. Structural analyses reveal the mechanisms of caspase-4 substrate recruitment and NAD⁺-dependent arginine ADP-riboxanation by OspC3.

Determination of the high-resolution structure of yeast TORC1 allows characterization of the precise interfaces of interaction between inactive TORC1 and TORC1′ polymers and identification of the mode of binding of active EGOC on TORC1.

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.

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.

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.

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.

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.

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.

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.

The flagella of mammalian sperm display non-planar, asymmetric beating, but the molecular basis is unclear. Chen et al. performed in situ cryo-ET of mouse and human sperm and discovered asymmetric distributions of regulatory complexes that could generate asymmetric bending force.

Renner et al. show that HIV-1 concentrates the metabolite IP6 into its virions to catalyze assembly of its iconic conical capsid. Disabling this enrichment mechanism prevents assembly and renders HIV-1 non-infectious.

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.