Volume 29 Issue 3, March 2022

The class II phosphatidylinositol 3-kinases (PI3Ks) serve important roles in diverse cellular processes. The lab of Volker Haucke has now determined high-resolution structures of mouse PI3KC2α in both active and inactive conformations, elucidating the autoregulatory mechanism of class II PI3K activation.

AlphaFold2 predictions, X-ray crystallography and cryo-EM analyses reveal how related human glycoproteins GP2 and uromodulin catch pathogenic bacteria by presenting a high-mannose glycan that acts as a decoy for fimbrial adhesin FimH.

Arlt et al. report a structure of yeast seipin, a lipid droplet formation protein, and suggest that it forms a flexible, oligomeric cage in the endoplasmic reticulum membrane, enabling triacylglycerol phase separation, lipid droplet growth and budding toward the cytoplasm.

Cryo-EM structures of the human pentameric glycosylphosphatidylinositol transamidase (GPIT) complex reveal its subunit assembly and its catalytic and GPI-binding sites.

Cryo-EM structures of somatostatin 14- and octreotide-bound somatostatin receptor 2 reveal a flexible extracellular domain for recognizing different ligands and, together with functional assays, identify the basis of SSTR subtype selectivity.

High-resolution structures of phosphatidylinositol 3-kinase (PI3K) type IIa unravel a coincident mechanism of lipid-induced enzyme activation and enable the development of inhibitors of class II PI3K function with applications in biomedicine.

HDX–MS analysis reveals the SARS-CoV-2 spike ectodomain reversibly samples an open-trimer conformation that reveals epitopes for a pan-coronavirus antibody; interconversion with the prefusion conformation is modulated by temperature, ACE2 receptor binding, and sequence variants.

Here the authors show that Xist drives non-stoichiometric recruitment of SHARP/SPEN to the inactive X chromosome, including at regions not occupied by Xist, through concentration-dependent homotypic assemblies of SHARP, which is required for chromosome-wide silencing. This spatial amplification allows Xist to balance chromosome-wide silencing and specificity to the X thereby enabling Xist to silence the X, the whole X, and nothing but the X.

In their complex, the SARS-CoV-2 nsp13 helicase and RNA polymerase would translocate on RNA in opposite directions. Cryo-EM and MD simulations resolve this conundrum, suggesting an allosteric mechanism to turn the helicase on and off.

Biochemical and cellular assays show that the S. cerevisiae SAGA complex undergoes acetylation-dependent dimerization that enables the transcriptional coactivator to cooperatively acetylate nucleosomes, facilitate gene transcription and increase cell survival under stress conditions.

The cryo-EM structure and functional analyses of oxytocin bound to its receptor reveal a Mg²⁺ coordination complex in the binding pocket and find that the identity of a single residue determines whether a vasopressin/oxytocin family receptor requires Mg²⁺ as a cofactor.