Understanding how a plant protein switch can mitigate water stress
Whether it be due to extreme heat, drought or flooding – climate change is having a devastating impact on plants. In fact, according to one study(opens in new window), as much as 16 % of plant species could lose more than 90 % of their range – placing them at a high risk of extinction. But this future isn’t written in stone. Through evolutionary adaptation, plants can increase their chance of survival. To illustrate, consider how plant cells utilise the PYL1 receptor protein. “By sensing abscisic acid, a plant hormone that accumulates during water shortages, this receptor can help a plant adapt to drought conditions,” explains Max Stammnitz, a staff scientist at the Centre for Genomic Regulation(opens in new window). This is but one example of how a plant can use a molecular switch to better respond to a changing environment. “While many biological systems depend on molecular switches, we still do not fully understand how their signal-processing properties are encoded in protein sequence,” adds Stammnitz. With the support of the EU-funded DeepGlue project, Stammnitz aimed to find out. “We wanted to know how mutations encode the behaviour of allosteric hormone receptors, those proteins that convert chemical signals into cellular responses,” he says. The project, which received support from the Marie Skłodowska-Curie Actions(opens in new window) programme, applied an experimental approach that allowed researchers to quantify how thousands of mutations alter the full dose-response behaviour of the receptor. In total, more than 40 000 quantitative measurements were generated, resulting in a near-complete map of how amino-acid changes tune the receptor’s activation function.
How mutations alter a receptor protein’s behaviour
Based on this work, researchers found that close to 90 % of mutations altered the PYL1 hormone receptor’s dose-response behaviour – often changing sensitivity, basal activity and maximum response in correlated ways. They also found that many of these effects can be explained by changes in receptor protein stability. “We showed how mutations can tune not just whether a receptor protein works, but how it responds across a chemical inducer concentration range,” remarks Stammnitz. The project also discovered that, beyond protein stability effects, individual signalling parameters can be tuned independently, including by allosteric mutations far from the protein-hormone interface. Perhaps most strikingly, rare single amino-acid substitutions also produced qualitatively new behaviours, including inverted and band-stop activation functions. More details on the project’s results can be found in an article published in ‘Nature Communications’(opens in new window).
Research could support climate-resilient agriculture
According to Stammnitz, DeepGlue has conceptually shown that protein switches aren’t ‘rigid devices’ but can be evolutionarily malleable systems whose quantitative behaviour can be extensively reshaped by mutation. “Our work provides a framework and dataset for engineering allosteric receptors and for interpreting how genetic sequence variation affects cellular signalling,” he says. This framework could be of particular interest to agriculture, helping farmers with a new generation of climate-resilient crops. “Several academic and industry groups around the world are already trying to better understand and engineer these molecular responses in the context of climate change,” concludes Stammnitz. The researchers are currently scaling up their deep mutational scanning experiments to compare the dose-response characteristics of mutants across several chemically inducible protein systems.
