Selected Grantee Publications
- Clear All
- 2 results found
- Microscopy
- 2023
Broad Receptor Tropism and Immunogenicity of a Clade 3 Sarbecovirus
Lee et al., Cell Host and Microbe. 2023.
https://www.sciencedirect.com/science/article/pii/S1931312823004225
Investigators showed that the S glycoprotein of the clade 3 sarbecovirus PRD-0038 in the African Rhinolophus bat has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. They generated a cryogenic electron microscopy structure of the RBD bound to ACE2, explaining receptor tropism and highlighting differences between SARS-CoV-1 and SARS-CoV-2. PRD‑0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses, compared with SARS-CoV-2. These findings underline a potential molecular pathway for zoonotic spillover of a clade 3 sarbecovirus, as well as the need to develop pan-sarbecovirus vaccines and countermeasures. Supported by ORIP (S10OD032290, S10OD026959, S10OD021644), NIAID, NCI, and NIGMS.
An E1–E2 Fusion Protein Primes Antiviral Immune Signaling in Bacteria
Ledvina et al., Nature. 2023.
https://www.nature.com/articles/s41586-022-05647-4
Investigators show that the cGAS/DncV–like nucleotidyltransferase (CD‑NTase)–associated protein 2 (Cap2) primes bacterial CD-NTases for activation through a ubiquitin transferase–like mechanism. A cryo-electron microscopy structure of the Cap2-CD-NTase complex reveals Cap2 as an all-in-one ubiquitin transferase–like protein, with distinct domains resembling eukaryotic E1 and E2 proteins. The structure captures a reactive-intermediate state with the CD-NTase C terminus positioned in the Cap2 E1 active site and conjugated to AMP. Cap2 conjugates the CD-NTase C terminus to a target molecule that primes the CD-NTase for increased cGAMP production. The investigators further demonstrate bacteria control immune signaling using an ancient, minimized ubiquitin transferase–like system and provide insight into the evolution of the E1 and E2 machinery across domains of life. Supported by ORIP (S10OD023498, S10OD021527, S10OD025267) and NIGMS.