A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients (12) and heathy patients (6), we identified three immunodominant linear epitopes, two of which correspond to key proteolytic sites on the spike protein (S1/S2 and S2’) known to be critical for cellular entry. We show biochemical evidence that plasma positive for the epitope adjacent to the S1/S2 cleavage site inhibits furin-mediated proteolysis of spike.

ESCRTing lenses away from senescence: ESCRT proteins control membrane fusion in various key cellular processes, but the mechanisms involved are still incompletely understood. Gulluni et al . report that ESCRT recruitment at the cytokinetic bridge is mediated by the binding of an ESCRT-II subunit to the signaling lipid phosphatidylinositol 3,4-bisphosphate (see the Perspective by Brill and Wilde). This pathway acts in parallel to a known cascade driven by a protein called ALIX, but its failure is sufficient to lead to premature senescence in the lens of fish, mouse, and human eyes, where ALIX is expressed at lower levels. These results point to an evolutionarily conserved pathway for the cell-specific control of cytokinesis that serves to protect from senescence and the early onset of cataracts. —SMH

The structure of class IB PI3K (p110γ-p101) reveals mechanism of GPCR activation and differences from class IA PI3Ks.

Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.