The control of protein arginine phosphorylation facilitates proteostasis by an AAA+ chaperone protease system

Abstract

We could demonstrate that the AAA+ unfoldase ClpC together with the protein arginine kinase and adaptor protein McsB, its activator McsA and the phosphatase YwlE form a unique chaperone system. Here, the McsA-activated McsB phosphorylates and targets aggregated substrate proteins for extraction and unfolding by ClpC. Sub-stoichiometric amounts of the YwlE phosphatase enhanced the ClpC/McsB/McsA mediated disaggregation and facilitated the de-phosphorylation of the arginine-phosphorylated substrate protein extruded by ClpC, allowing its subsequent refolding. Interestingly, the successfully refolded protein escaped degradation by the loosely associated ClpP protease. This unique chaperone system is thereby able to disaggregate and refold aggregated proteins but can also remove severely damaged protein aggregates by degradation.