In this issue of Structure, Shaw et al.1 visualize the PI4KA-TTC7B-FAM126A-calcineurin complex by combining cryo-EM, HDX-MS, and AlphaFold3, and reveal a dual interaction of calcineurin with PI4KA and FAM126A. This work promotes our understanding of calcineurin-regulated PI4KA activity and paves the way for further exploration of the roles of PI4KA in the plasma membrane.

G protein-coupled receptors (GPCRs) orchestrate many physiological functions and are a crucial target in drug discovery. Adhesion GPCRs (aGPCRs), the second largest family within this superfamily, are promising yet underexplored targets for treating various diseases, including obesity, psychiatric disorders, and cancer. However, the receptors’ unique and complex structure and miscellaneous interactions

In this issue of Structure, Dey et al.1 employ single-molecule FRET to map the conformational trajectory of Omicron spikes during fusion, revealing a transition from pre-fusion to post-fusion through two intermediates. This study highlights the roles of acidic environments, Ca2+, and receptors in promoting SARS-CoV-2 cell entry.

The enzymatically regioselective catalyzed incorporation of cysteine sulfoxide into histidine generates physiologically important antioxidants such as ergothioneine and ovothiol. In this issue of Structure, Ireland et al.1 report the crystal structure of EgtB-IV, which provides insights into the convergent evolution of sulfoxide synthase.

Phosphorylation of ubiquitin and the ubiquitin-like domain of Parkin, mediated by the kinase PINK1, is essential for the liberation of the E3 ligase from its autoinhibited state. In this issue of Structure, Lenka et al.1 provide the structural basis for the specificity and stronger Parkin activation by phospho-NEDD8 compared to phospho-ubiquitin.

(Structure 32, 1–16; November 7, 2024)

(Structure 32, 1–15; December 5, 2024)

In this issue of Structure, Fan et al.1 report the structure of the full contactin 2 ectodomain, representing the first for the contactin family. The work reveals six immunoglobulin domains are essential for intercellular interactions, explores differences in proposed contactin 2 homodimerization mechanisms, and provides an updated model for contactin 2 organization on and between cells.

In this issue of Structure, Soeda et al.1 employed optogenetic tools and demonstrate that an N-terminal truncation of tau and microtubule-binding deficiency lead to the formation of tau condensates, accelerating its fibrillation.

In this issue of Structure, Cao et al.1 use X-ray crystallography, biochemical, and genetic studies to define the key role of the Mind bomb-1 ccRING3 domain in triggering Notch signaling, and they demonstrate that ccRING3-mediated dimerization is a key step in ligand activation.

In a recent issue of Nature, Chambers et al.1 combined bioinformatics, biochemistry, and X-ray crystallography to uncover the presence of a ubiquitin-like machinery in bacteria, which was believed to be unique to archaea and eukaryotes. This study highlights the prevalence of a ubiquitin-like system in bacteria that was later adopted by the eukaryotes for various purposes such as protein degradation

Recent advancements in RNA three-dimensional (3D) structure prediction have provided significant insights into RNA biology, highlighting the essential role of RNA in cellular functions and its therapeutic potential. This review summarizes the latest developments in computational methods, particularly the incorporation of artificial intelligence and machine learning, which have improved the efficiency