The dynamic interactome of human Ahal upon Y223 phosphorylation

Heat Shock Protein 90 (Hsp90) is an essential chaperone that supports the function of a wide range of signaling molecules. Hsp90 binds to a suite of co-chaperone proteins that regulate Hsp90 function through alteration of intrinsic ATPase activity. Several studies have determined Ahal to be an important co-chaperone whose binding to Hsp90 is modulated by phosphorylation, acetylation and SUMOylation of Hsp90 [1,2]. In this study, we applied quantitative affinity-purification mass spectrometry (AP-MS) proteomics to understand how phosphorylation of hAhal at Y223 altered global client/co-chaperone interaction [3]. Specifically, we characterized and compared the interactomes of Ahal-Y223F (phospho-mutant form) and Ahal-Y223E (phosphomimic form). We identified 99 statistically significant interactors of hAhal, a high proportion of which (84%) demonstrated preferential binding to the phospho-mimic form of hAhal. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository [4] with the dataset identifier PXD001737. (C) 2015 The Authors. Published by Elsevier Inc.