A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors

Abstract

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 via 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 signaling.

Structural insights into PYR/PYL/RCAR ABA receptors and PP2Cs

“…Additionally, (-)ABA promoted interaction of PYL2, PYL3 and PYL4 with HAB1 [8]. Structural studies on PYL2 also show that the minus enantiomer can be accommodated into the ABA-binding pocket [19], although the dimethyl group flipped in the (-)enantiomer would cause some steric hindrance with the narrow pocket that accommodates the monomethyl group [15].…”

“…For instance, apoPYL1 [15], apoPYL2 [15,19], ABA-bound PYL1 [16] and ABA-bound PYL2 [15,19] structures have been resolved. In the case of PYR1, in the crystallographic asymmetric unit, there is one ABA-bound and one ABA-free subunit [17,18].…”

“…The structure of the ABA-bound forms of PYR1, PYL1 and PYL2 reveals the nature of the interactions stabilizing the hormone into the receptor binding pocket [15,16,17,18,19]. The ABA sits in a deep cavity almost completely buried from the external medium (see figure 3).…”

“…The PYR/PYL/RCAR family of ABA receptors has witnessed a rapid explosion of structural data, since five independent groups have reported structural and functional mechanisms on ABA signaling [15,16,17,18,19], and even more recently, using the seed ABA-agonist pyrabactin (Fig. 1C), the structural basis for selective activation of certain receptors and the mechanism of antagonism in other members [20,21,22].…”

ABA signalling is fine-tuned by antagonistic HAB1 variants

“…ABA binds to PYLs, promoting their interaction with PP2Cs and inhibiting their phosphatase activity [5][6][7] . Thus, SnRK2s are released from PP2C-SnRK2 complexes to phosphorylate downstream effectors and activate ABA signalling 3,5,6,[8][9][10] . Over the past several years, the structures and molecular functions of ABA receptors have received significant attention [9][10][11] .…”