As a model for Intrinsically Disordered Region (IDR) structure-function, we investigated the IDR present in the E. coli chemotaxis regulatory phosphatase CheZ. The CheZ IDR (amino acids 169-200) is attractive for study because CheZ is part of an exceptionally well characterized and easily tractable system and has an available high-resolution crystal structure. The CheZ IDR contains striking evolutionarily conserved regions that are functionally critical as shown by the fact that changes in single specific amino acids in the conserved IDR regions are able to abolish normal chemotaxis. We have focused on identifying suppressor mutations in the coding region of CheZ G188E, a variant with a >80% reduction in chemotactic swarm activity. Our screen identified 6 suppressor mutations that restored swarm activity to wild-type levels. Interestingly, the suppressor mutations were found not in the CheZ coding region, but in CheY, the phosphoprotein substrate of the CheZ phosphatase. The 6 suppressor mutations were restricted to two amino acid codons. Three suppressor mutations were found at position CheY A42 and three at position CheY M60. A model for how the changes in CheY restore CheZ activity is presented. These studies in dissection of the CheZ IDR will be useful in extending our understanding of IDR structure-function. The accumulating knowledge of IDR principles will be a significant component of a broadening understanding of protein biophysics with direct implications in basic protein structure and protein engineering research.