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🧵 After years out of the field, I and my lab are again working on bacterial type IV pili. We have just posted our first preprints, and I'm excited to share what we have discovered. This shows Neisseria gonorrheae bacteria infecting a human epithelical cell. Here, you can see the pili in red. 1/

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4 прямых ответов · 23 сообщений

A typo in the first post. *Epithelial.* Edit button, please, @bsky.app

In this thread I'll call type IV pili "T4P." T4P are thin protein filaments assembled from the plasma membrane of diverse bacteria. They are typically ~6 nm in diameter, and can be over 10 µm long. 2/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

T4P are found across the Bacteria, in both Gram positive and negative species, and are also present in Archea. They are so widespread and diverse that it's thought they were present in the Last Universal Common Ancestor (LUCA) of all life on earth. doi.org/10.1371/jour... 3/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

The fibers are polymers, assembled by a subunit called pilin. Pilin is an integral membrane protein. The fibers are assembled from the pool of pilin monomers in the membrane. They are dynamic — they both polymerize and depolymerize, retracting into the membrane. 4/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

A "basal body" machine drives these processes. Electron tomography and sub-tomogram averaging have begun to provide a picture of how this works. This is from a beautiful recent paper from Jun Liu, @dr-lori-burrows.bsky.social and colleagues. doi.org/10.1038/s414... 5/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

Subunits are added and removed from the fiber's base, so the first thing made is the tip — and it is special. It is a cap of proteins called minor pilins. The tip complex has (at least) two functions: • It controls fiber initiation • It anchors adhesins that allow pili to stick to targets. 6/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

If you think about eukaryotes more than prokaryotes, this analogy may be useful. We think the tip complex is like the Arp2/3 and γ-tubulin complexes that nuleate microtubule and actin polymerization. A complex of proteins related to the main protomer templates the formation of the filament. 7/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

Initiation complexes also serve as points of regulation — cells tell them when and where to initiate polymerization. But how does this work for T4P filaments? 8/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

Unfortunately, we don't have experimentally determined structures of any T4F tip complexes. For example, here is a recent EM tomography model. The tip complex is the purple thing. doi.org/10.1038/s414... 9/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

But AlphaFold makes a remarkable — and more importantly — testable set of predictions! 10/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

Looking down on the fiber, minor pilins I, J, and K are arranged in clockwise order. The tip adhesin (purple) is called PilC or PilY1. We'll call it PilC/Y1 here. And the last 6-10 amino acids of PilC/Y1 (shown in black) shoot right down the bore of the minor pilin I/J/K trimer. 11/

Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

wow. that's cool! (and I did not know it)

adding my sincere appreciation for this thread and a recent article of ours where TFP play a key role as phage receptor 😉 www.cell.com/current-biol...

Filamentous cheater phages drive bacterial and phage populations to lower fitnessKubota et al. show that bacteria can use their filamentous phage to outcompete other bacteria, but increased phage production enables the evolution of cheater miniphages with truncated genomes. Miniph...www.cell.com
Ответ для Vaughn Cooper

I love this paper, and want to add a little nugget from our work on conjugative pilus-dependent phages, in which we found a repeated evolutionary relationship between phages targeting the T4P and T4SS: (two paragraphs, search for T4P, also one of them in FigS3) www.nature.com/articles/s41...

Diverse and abundant phages exploit conjugative plasmids - Nature CommunicationsSome phages use plasmid-encoded conjugation proteins as receptors to infect their bacterial hosts, making their host range dependent on horizontal transfer of the plasmid. Here, the authors present a ...www.nature.com
Ответ для Michael Baym

Pili everywhere!!!

Ответ для Jen Herman 🌪️
woody and buzz lightyear from toy story are standing next to each other and saying `` everywhere ! ''ALT: woody and buzz lightyear from toy story are standing next to each other and saying `` everywhere ! ''media.tenor.com
Ответ для Michael Baym
Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦
Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

Gorgeous

Ответ для Michael Baym
Ответ для Alex Merz 🇺🇸🇨🇦🇺🇦

the OG discovery!

👍