Dynamic control of RSK complexes by phosphoswitch‐based regulation

• DOI: 10.1111/febs.14311
• Publication Date: 2017-10-30T14:52:41Z
• Authors: Gergő Gógl; Beáta Biri‐Kovács; Ádám L. Póti; Henrietta Vadászi; Bálint Szeder; Andrea Bodor; Gitta Schlosser; András Ács; Lilla Turiák; László Buday; Anita Alexa; László Nyitray; Attila Reményi
• Keywords: PDZ domain; C-terminus

Assembly and disassembly of protein-protein complexes needs to be dynamically controlled phosphoswitches based on linear motifs are crucial in this process. Extracellular signal-regulated kinase 2 (ERK2) recognizes a linear-binding motif at the C-terminal tail (CTT) ribosomal S6 1 (RSK1), leading phosphorylation subsequent activation RSK1. The CTT also contains classical PDZ domain-binding which binds RSK substrates (e.g. MAGI-1). We show that autophosphorylation disordered promotes formation an intramolecular charge clamp, efficiently masks critical residues indirectly hinders ERK binding. Thus, RSK1 operates as autoregulated phosphoswitch: its specific sites affects protein-binding capacity conformational dynamics. These biochemical feedbacks, form structural basis for rapid dissociation ERK2-RSK1 RSK1-PDZ substrate under sustained epidermal growth factor (EGF) stimulation, were structurally characterized validated living cells. Overall, changes induced by regions protein kinases, coupled allosteric events occurring domain cores, may provide mechanisms contribute emergence complex signaling activities. In addition, we can functionally classified ON OFF interaction switches or dimmers, depending positioning target relation functional motifs. Moreover, phosphorylated with positively charged is likely common mechanism phosphoregulation.Structural data available PDB database accession numbers 5N7D, 5N7F 5N7G. NMR spectral assignation BMRB 27213 27214.