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ARS Home » Midwest Area » Urbana, Illinois » Global Change and Photosynthesis Research » Research » Publications at this Location » Publication #340900

Title: Allosteric control of a plant receptor kinase through S-glutathionylation

item MOFFETT, ALEXANDER - University Of Illinois
item BENDER, KYLE - University Of Illinois
item Huber, Steven
item SHUKLA, DIWAKER - University Of Illinois

Submitted to: Biophysical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2017
Publication Date: 12/5/2017
Citation: Moffett, A.S., Bender, K.W., Huber, S.C., Shukla, D. 2017. Allosteric control of a plant receptor kinase through S-glutathionylation. Biophysical Journal. 113(11):2354-2363.

Interpretive Summary: Glutathione (GSH) is a peptide present in most known life forms, responsible for regulating cellular redox state. GSH is known to form disulfide bonds with protein cysteine residues and affect protein function, and there is evidence that a range of protein kinases in several different organisms can be glutathionylated, which could be a specific input channel for integration of redox information into cellular signaling. Receptor-like kinases (RLKs) play a critical role in plant growth and development, receiving and transducing hormonal signals into the language of cellar signaling cascades. A recent study provides evidence that the Arabidopsis thaliana RLK Brassinosteroid.

Technical Abstract: Growing evidence supports the importance of protein S-glutathionylation as a regulatory post-translational modification with functional consequences for proteins. Discoveries of protein kinase S-glutathionylation have fueled discussion of redox signaling, where changes in cellular redox state can feed directly into cellular signaling pathways through redox-state-dependent kinase modification. Following previously published experimental evidence for S-glutathionylation induced deactivation of the Arabidopsis thaliana brassinosteroid insensitive 1 (BRI1)-associated receptor-like kinase 1 (BAK1), we investigate the consequences of S-glutathionylation on the equilibrium conformational ensemble of BAK1 using all atom molecular dynamics simulations. We find that glutathionylation of C408 just below the aC helix allosterically destabilizes the active-like state of BAK1 while stabilizing an inactive conformation known to recur in protein kinases. Glutathionylation of C408 also has structural consequences throughout the BAK1 kinase domain, while glutathionylation of C353 in the N-lobe and C374 near the ATP binding site have few notable effects on BAK1 as compared to the unmodified kinase. Our results support the notion of kinase S-glutathionylation as a channel for redox information provided that the modification happens in the first place, providing a plausible molecular mechanism for allosteric control of kinases through S-glutathionylation which could be present in other kinases.