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ToolsMühlenbeck, Henning, Tsutsui, Yuko, Lemmon, Mark A., Bender, Kyle W. and Zipfel, Cyril (2024) Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling. eLife, 12. ISSN 2050-084X
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Abstract
Transmembrane signaling by plant receptor kinases (RKs) has long been thought to involve reciprocal trans-phosphorylation of their intracellular kinase domains. The fact that many of these are pseudokinase domains, however, suggests that additional mechanisms must govern RK signaling activation. Non-catalytic signaling mechanisms of protein kinase domains have been described in metazoans, but information is scarce for plants. Recently, a non-catalytic function was reported for the leucine-rich repeat (LRR)-RK subfamily XIIa member EFR (elongation factor Tu receptor) and phosphorylation-dependent conformational changes were proposed to regulate signaling of RKs with non-RD kinase domains. Here, using EFR as a model, we describe a noncatalytic activation mechanism for LRR-RKs with non-RD kinase domains. EFR is an active kinase, but a kinase-dead variant retains the ability to enhance catalytic activity of its co-receptor kinase BAK1/ SERK3 (brassinosteroid insensitive 1-associated kinase 1/somatic embryogenesis receptor kinase 3). Applying hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis and designing homology-based intragenic suppressor mutations, we provide evidence that the EFR kinase domain must adopt its active conformation in order to activate BAK1 allosterically, likely by supporting αC-helix positioning in BAK1. Our results suggest a conformational toggle model for signaling, in which BAK1 first phosphorylates EFR in the activation loop to stabilize its active conformation, allowing EFR in turn to allosterically activate BAK1.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability statement: All HDX RAW data for wild type and Y836F EFR have been deposited to the ProteomeXchange Consortium via ProteomeXchage via the PRIDE (Perez-Riverol et al., 2022) with the dataset identifier PXD049215. Supplemental information, including plasmid maps, replication information, cropping information, gene IDs, protein sequences, and PDB files, are available through a Zenodo repository (https://doi.org/10.5281/zenodo.10577812). Funding Information: This project was funded by the University of Z\u00FCrich (C.Z.), the Swiss National Science Foundation grant no. 31003 A_182625 (C.Z.), a joint European Research Area Network for Coordinating Action in Plant Sciences (ERA-CAPS) grant (\u2018SICOPID\u2019) from UK Research and Innovation (BB/S004734/1) (C.Z.), and by NIH grant R35-GM122485 (M.A.L.). |
| Uncontrolled Keywords: | neuroscience(all),biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2800 |
| Faculty \ School: | Faculty of Science > The Sainsbury Laboratory |
| UEA Research Groups: | Faculty of Science > Research Groups > Plant Sciences |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 31 Oct 2024 09:30 |
| Last Modified: | 01 Nov 2024 00:53 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97354 |
| DOI: | 10.7554/eLife.92110 |
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