Inlay

This work was a collaboration with Collin Chiu, @maxewilkinson.bsky.social, and a great team!

I am so excited to share our new findings with you! We provide the structural evidence for a direct protein-to-DNA information pathway, showing how a bacterial enzyme 'reads' its own structure to 'write' DNA. www.science.org/doi/10.1126/...

Protein-templated DRT3 expands the textbook definition of reverse transcriptases further! Beautiful paper led by Pujuan Deng, Hyunbin Lee, and Carlo Armijo!

I’m thrilled to share our work on phage triggers of the bacterial immune system in its final form @natmicrobiol.nature.com www.nature.com/articles/s41...

Excited to share our preprint on terminase sensing by Avs2 and Upx! We solved a cryo-EM structure of Avs2 with terminase and found an unexpected "bridging" ATP at their interface. In contrast, Upx is predicted to bind an unfolded ATPase domain via β-augmentation. www.biorxiv.org/content/10.6...

With Eugene Koonin, we wrote a rather comprehensive review on the origin, evolution and organization of the #virosphere. We describe all 10 viral realms and the logic behind them, and so much more. Check it out! comptes-rendus.academie-sciences.fr/biologies/ar...

Amazing findings in geometry-based immune activation! Two bacterial defence systems detect phage-encoded ring oligomers, assemble high-order molecular complexes, and trigger abortive infection. www.nature.com/articles/s41... www.nature.com/articles/s41...

NLR-like immunity in bacteria A new study from the Alex Gao lab. The scope of this work is incredible!!! www.biorxiv.org/content/10.6...

Prokaryotes employ diverse defense strategies to detect and halt the progression of phage infection. Multiple defense systems sense phage proteins through direct binding, including antiviral STAND NTPases (Avs), which oligomerize upon target recognition to induce programmed cell death. The widespread Avs2 family was previously shown to detect the large terminase subunit of tailed phages, but the mechanism of terminase sensing was unknown. Here, we determine the structural basis of terminase recognition by Avs2 from Escherichia coli (EcAvs2). A cryo-EM structure at 2.3 Å resolution reveals that EcAvs2 forms a flat, C4-symmetric tetramer in which each protomer is bound to a single terminase monomer. Terminase recognition is mediated by a large, shape complementary binding pocket in the EcAvs2 sensor domain, including specific contacts with an unexpected ATP molecule at the interface of EcAvs2 and terminase. Furthermore, we demonstrate that the defense protein Upx also recognizes diverse phage terminases, despite lacking sequence and structural homology to Avs. AlphaFold 3 models indicate that Upx binds an unfolded state of the core terminase ATPase domain, mediated by β-augmentation. These findings highlight the distinct modes of terminase recognition across structurally diverse defense proteins. ### Competing Interest Statement F.Z. is a scientific advisor and cofounder of Beam Therapeutics, Pairwise Plants, Arbor Biotechnologies, Aera Therapeutics, and Moonwalk Biosciences. F.Z. is a scientific advisor for Octant. The remaining authors have no competing interests to declare. National Institute of General Medical Sciences, 5T32GM007276, 5T32GM141828 Stanford Bio-X Helen Hay Whitney Foundation, https://ror.org/037ebw447 Howard Hughes Medical Institute, https://ror.org/006w34k90 Yang Tan Collective K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center Broad Institute Programmable Therapeutics Donors BT Charitable Foundation G. Harold & Leila Y. Mathers Foundation, MF-2303-04116 Stanford University School of Medicine, https://ror.org/011pcwc98

Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed. In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts. www.biorxiv.org/content/10.6...

Vaults. They are cell biology's greatest puzzle! This preprint from Martin Beck's lab shows them docked on ER membranes with a ribosome inside. What on earth is going on there?? #CellBiology #WTFology www.biorxiv.org/content/10.6...

Recognition of foreign molecules inside cells is critical for immunity in all domains of life. Proteins of the STAND NTPase superfamily, including eukaryotic nucleotide-binding oligomerization domain ...