Intrinsically disordered but biologically active proteins, commonly referred to as IDPs, are readily identified in many biological systems and play critical roles in multiple protein regulatory processes. While disordered in their unbound states, IDPs often, but not always, fold upon binding with their protein interaction partners. Here, we discuss how a class of IDPs directs the targeting, specificity and activity of Protein Phosphatase 1 (PP1). PP1 is major ser/thr phosphatase that plays a critical role in a broad range of biological processes, from muscle contraction to memory formation. In the cell, PP1 is regulated through its interaction with more than 200 regulatory proteins, the majority of which are IDPs. Critically, these PP1:regulatory protein holoenzyme complexes confer specificity to PP1 and are thus the functional forms of the PP1 enzyme in vivo. Furthermore, we discuss the distinct modes of interaction utilized by IDPs to complex with their protein binding partners. We subsequently show, by integrating multiple biophysical tools, that the majority of IDPs that regulate PP1, prefer a conformational selection model.
Keywords: Intrinsically disordered proteins, Proteins, Protein phosphatase 1, Folding, crystallography, SPINOPHILIN, C-terminus, INHIBITOR-2, holoenzyme, macromolecule
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