Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2–ABA–PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a gate that closes in response to ABA by way of conformational changes in two highly conserved β-loops that serve as a gate and latch. Moreover, ABA-induced closure of the gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the gate and latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved gate–latch–lock mechanism underlying ABA signalling.
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Protein Data Bank
The structure factors and atomic coordinates discussed in this work have been deposited in the Protein Data Bank. The accession codes are: 3KAY for apo-PYL1; 3KAZ for apo-PYL2; 3KB0 for the ABA-bound PYL2 complex; and 3KB3 for the ternary complex of PYL2–ABA–HAB1.
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We thank the staff of LS-CAT for assistance in data collection at the beam lines of sector 21, which is in part funded by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor. Use of the Advanced Photon Source was supported by the Office of Science of the US Department of Energy. This work was supported by the Jay and Betty Van Andel Foundation (H.E.X.), the National Institutes of Health (H.E.X., B.F.V. and J-K. Z.), and the National Science Foundation (S.R.C.). L.-M.N. and F.-F.S. were supported by an overseas PhD scholarship from the NUS Graduate School for Integrative Sciences & Engineering (NGS).
Author Contributions K.M., Jun Li, Jiayang Li, E.-L.Y., B.F.V., S.R.C., J.-K.Z. and H.E.X. conceived the project and designed research; K.M., L.-M.N., X.E.Z., F.-F.S., Y.X., K.M.S.-P., S.-Y.P., J.J.W., H.F., V.C., A.K., Y.W., F.C.P., D.R.J. and H.E.X. performed research; K.M., L.-M.N., X.E.Z., F.-F.S., Y.X., K.M.S.-P., S.-Y.P., J.J.W., H.F., V.C., B.F.V., S.R.C., J.-K.Z. and H.E.X. analysed data; and K.M., S.R.C. and H.E.X. wrote the paper with contributions from all authors.
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Melcher, K., Ng, L., Zhou, X. et al. A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors . Nature 462, 602–608 (2009). https://doi.org/10.1038/nature08613
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