laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026I’d also like to thank all of the other authors, our collaborator @kevincorbett.bsky.social, the entire Whiteley lab, and especially @aaronwhiteley.bsky.social for all of the guidance along the way. 010
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026Lastly, I want to say a huge thank you to everyone who made this work possible. Thank you to the two other first authors, @emilykibby.bsky.social and @amardeeep.bsky.social, both of whom contributed an enormous amount to this project. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026I’ll be at #SISB2026 this week if anyone wants to chat more about these findings at my poster on Wednesday (B21). I’m looking forward to meeting many of you for the first time! 110
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026The C-terminus, separate from the large oligomerization interface, reaches to an adjacent protomer to stabilize the full complex. Multiple oligomerization interfaces have also been observed in related plant systems, perhaps one way these systems are mechanistically similar across the tree of life. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026Our discussion section has the full story, but one point I am most excited about is our observation of how these domains cooperate to form an activated complex. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026In addition to being an exciting mechanism, we believe that this work provides insights into why NACHT and related P-loop NTPase domains are such abundant immune components across the tree of life. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026We found that bNACHT11 re-localizes following activation and initiates plasmolysis, a process where the inner membrane collapses due to outward osmotic flux of water. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026Finally, we turned out attention to the effector mechanism of bNACHT11. Based on other STAND NTPases, we expected the N-terminus to mediate programmed cell death, but how does this short ~45 amino acid region kill bacteria? 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026We next investigated the functions of these phage proteins and found that three activators each bind a different host kinase in the absence of bNACHT11. This suggests that these proteins are not only distinct in their sequence and structure, but also by their function. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026Observing this interaction in an immune receptor is exciting because these interactions are agnostic to the amino acid sequence. This likely contributes to the breadth of sensing and limits the possible mutations that allow for pathogen escape. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026β-augmentation describes when a β-strand from one protein forms an anti-parallel β-sheet with a β-strand from another protein. β-augmentation was found at the interface of bNACHT11 and each of the other phage protein activators. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026This structure revealed bNACHT11 forms a heptamer when activated, and that interactions between bNACHT11 and gp57 are mediated through a hydrophobic pocket and β-augmentation. 100
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026We wanted to better understand how bNACHT11 accomplishes this sensing feat. In collaboration with the Corbett Lab at UCSD, @amardeeep.bsky.social determined a cryoEM structure of bNACHT11 activated by the phage protein T2 gp57. 110
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026Previously, we identified phage protein activators of bNACHT11 using a high throughput AlphaFold screen. Some phages even encode up to 5 proteins capable of activating bNACHT11! Remarkably, these proteins directly bind bNACHT11 despite sharing no similarity in their sequence or predicted structure. 121
laurelrobbins.bsky.social @laurelrobbins.bsky.social · 05/05/2026I’m thrilled to share an update to our work on bacterial NACHT domain containing proteins! In our last preprint, we reported that bNACHT11 is activated by multiple phage proteins. We’ve now expanded this work with structural insight and investigation of programmed cell death following activation.biorxiv.org 23520
