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

Do other L-shaped effectors interact with TOLs and suppress NRCs? AVRcap1b orthologs from closely related Phytophthora are predicted to have an L-shape and bind NbTOL9a… but they cannot suppress NRCs! Seems like TOL binding is not sufficient for suppression.
10/15

Using the structure, we generated AVRcap1b mutants impaired in NbTOL9a binding and… You guessed it, they’re impaired in suppression as well. TOL binding is definitely required for this effector’s full virulence function.
9/15

We then solved the crystal structure of AVRcap1b in complex with the NbTOL9a ENTH domain (in green). Having the interaction interface was nice, but what was really cool was that AVRcap1b was completely different to other RXLR-LWY effectors! It exhibits a novel L-shaped structure.

AVRcap1b is a multidomain RXLR LWY effector, featuring one WY domain and six LWY domains. This arrangement is similar to the structurally characterized LWY effector, PSR2, from P. sojae, which exhibits a linear structure. Are AVRcap1b or other LWY effectors also linear 🤔?
5/15

One of the effectors we characterized was AVRcap1b, from the oomycete pathogen P. infestans. AVRcap1b did not interact with resting state NRCs but interacted with host protein NbTOL9a. We concluded that it was suppressing NRC-mediated signaling indirectly via NbTOL9a.
4/15

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