Structural basis for negative regulation of ABA signaling by ROP11 GTPase

Abscisic acid (ABA) is an essential plant hormone responsible for plant
development and stress responses. Recent structural and biochemical
studies have identified the key components involved in ABA signaling
cascade, including PYR/PYL/RCAR receptors, protein phosphatases PP2C, and
protein kinases SnRK2. The plant-specific, Roh-like (ROPs) small GTPases
are negative regulators of ABA signal transduction by interacting with
PP2C, which can shut off “leaky” ABA signal transduction caused by
constitutive activity of monomeric PYR/PYL/RCAR receptors. However, the
structural basis for negative regulation of ABA signaling by ROP GTPases
remain elusive. In this study, we have utilized large-scale coarse-grained
(10.05 milliseconds) and all-atom molecular dynamics simulations and
standard protein-protein binding free energy calculations to predict the
complex structure of AtROP11 and phosphatase AtABI1. In addition, we have
elucidated the detailed complex association pathway and identified the
critical residue pairs in AtROP11 and AtABI1 for complex stability.
Overall, this study has established a powerful framework of using
large-scale molecular simulations to predict unknown protein complex
structures and elucidated the molecular mechanism of  negative
regulation of ABA signal transduction by small GTPases.