**Erik H. A. Rikkerink**

The New Zealand Institute for Plant & Food Research Ltd., 120 Mt. Albert Rd., Private Bag 92169, Auckland 1025, New Zealand; erik.rikkerink@plantandfood.co.nz; Tel.: +64-9-925-7157

Received: 8 February 2018; Accepted: 7 March 2018; Published: 8 March 2018

**Abstract:** Organisms face stress from multiple sources simultaneously and require mechanisms to respond to these scenarios if they are to survive in the long term. This overview focuses on a series of key points that illustrate how disorder and post-translational changes can combine to play a critical role in orchestrating the response of organisms to the stress of a changing environment. Increasingly, protein complexes are thought of as dynamic multi-component molecular machines able to adapt through compositional, conformational and/or post-translational modifications to control their largely metabolic outputs. These metabolites then feed into cellular physiological homeostasis or the production of secondary metabolites with novel anti-microbial properties. The control of adaptations to stress operates at multiple levels including the proteome and the dynamic nature of proteomic changes suggests a parallel with the equally dynamic epigenetic changes at the level of nucleic acids. Given their properties, I propose that some disordered protein platforms specifically enable organisms to sense and react rapidly as the first line of response to change. Using examples from the highly dynamic host-pathogen and host-stress response, I illustrate by example how disordered proteins are key to fulfilling the need for multiple levels of integration of response at different time scales to create robust control points.

**Keywords:** intrinsically disordered proteins; epiproteome; disordered protein platform; molecular recognition feature; post-translational modifications; physiological homeostasis; stress response; RIN4; p53; molecular machines
