Jogi Madhuprakash
jmadhuprakash.bsky.social
Jogi Madhuprakash
@jmadhuprakash.bsky.social
Thank you, JC! 😊
July 17, 2025 at 5:49 AM
Thank you, Sam!😊
July 17, 2025 at 3:33 AM
And a special shout-out to @kamounlab.bsky.social for his unwavering support on this journey exploring AVRcap1b from Phytophthora infestans – the infamous Irish potato famine pathogen. 🥔🦠
10/10
July 16, 2025 at 12:27 PM
Huge thanks to Ben and all our fantastic co-authors (‪@adelineharant.bsky.social @mpcontreras.bsky.social @Liang-Yu Hou @Chih-Hang Wu ‪@kamounlab.bsky.social‬) who made this story possible.
Here’s that amazing movie by Ben again!
9/10
July 16, 2025 at 12:27 PM
Our model: Once activated, dissociated NRC protomers assemble in a stepwise manner to form a full hexameric resistosome. AVRcap1b blocks this process, capturing NRC assembly intermediates and relocating them via the TOL-ESCRT pathway.
Effector biology rocks! #EffectorWisdom
8/10
July 16, 2025 at 12:27 PM
Remember TOL? How does it bind to AVRcap1b compared to SlNRC3? Turns out, they bind to opposite interfaces on AVRcap1b! This supports a dual-targeting mechanism, with the effector linking ‘immune suppression’ to ‘membrane trafficking’
🧊 SlNRC3–AVRcap1b (cryoEM)
🧬 AVRcap1b–TOL (PDB:9RDC)
7/10
July 16, 2025 at 12:27 PM
It turns out we could use AVRcap1b as a molecular trap to capture other NRC assembly intermediates. One AVRcap1b truncation captured an SlNRC3 assembly intermediate with four protomers.
Cool! NRC resistosomes assemble in a stepwise process!
6/10
July 16, 2025 at 12:27 PM
Through its L-shaped structure, AVRcap1b sterically blocks the SlNRC3 resistosome by forming contacts with three protomers (half the hexameric resistosome)!
5/10
July 16, 2025 at 12:27 PM
What’s this intriguing complex? Together with Ben, we purified the AVRcap1b-SlNRC3 complex from our favourite plant—the Aussie wonder Nicotiana benthamiana aka benthi—and resolved this beautiful cryo-EM structure and see how AVRcap1b wraps around three SlNRC3 protomers!
4/10
July 16, 2025 at 12:27 PM
What sort of complex does AVRcap1b form with activated NRCs? Blue Native-PAGE assays revealed an intermediate complex. Instead of the expected NRC hexamer, we saw an intriguing smaller band that contains both tomato NRC3 and Phytophthora AVRcap1b 🤔
3/10
July 16, 2025 at 12:27 PM
It turned out AVRcap1b associates only with the activated NRCs, but not their resting state. Check this super co-IP experiment from our previous paper:
bsky.app/profile/kamo...
2/10
A co-IP masterclass. Courtesy of Madhu
@jmadhuprakash.bsky.social
Here’s the major plot twist… AVRcap1b does not interact with resting-state NRCs but interacts specifically with the active form! It binds NRCs through a surface distinct from the NbTOL9a interface, suggesting it bridges these pathways to “block” immune signaling.
12/15
July 16, 2025 at 12:27 PM
We’re building on the recent structure of L-shaped AVRcap1b effector in complex with a host TOL9 protein. This effector bridges TOL9 and NRC helpers to suppress immunity 👇
bsky.app/profile/mpco...
2/10
Thrilled to share our latest preprint! This work started during my PhD and was finished together with @jmadhuprakash.bsky.social. We found a Phytophthora infestans L-shaped effector that bridges a host TOL protein to activated NLRs to suppress immunity!
www.biorxiv.org/content/10.1...
1/15
July 16, 2025 at 12:27 PM