Hypothetical models for effector recognition by CNL pairs
The upper box shows the secondary structure of a sensor CNL, with the ID at the C-terminus and a helper CNL, as well as the recognized effector. In the pre-activation state the sCNL and hCNL form an inactive complex with CC hetero-interactions. In certain pairs, such as RGA4/RGA5, the sNLR maintains the autoactive hNLR in a repressed state in this pre-activation complex. Binding of the effector to the sCNL is thought to trigger molecular rearrangements that activate the hetero-complex and induce the formation of a ZAR1-like resistosome where the hCNL CC domains self-associate. Model 1 assumes that the effector-bound sCNL is functionally analogous to the PBL2/RKS1 complex in the ZAR1 resistosome. In this model, the sCNL/effector complex associates to the periphery of the resistosome that is formed by the association of the hCNL into a pentameric wheel-like multimer. Model 2 implies that the sCNL is released from the pre-activation complex upon effector binding and that the resistosome is only composed of the hCNL. Finally, the sNLR could be part of the inner pentameric ring of the resistosome together with the hCNL as depicted in Model 3. In the case of ZAR1, the self-association of the CC domain in the resistosome creates a cation channel that inserts into in the plasma membrane and triggers calcium influx, immunity and cell-death. Such activity has not been reported for CNL pairs but sequence similarity between the CC domains of ZAR1 and hCLRs suggests that they could act by similar mechanisms.