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Regulated protein aggregation: a mechanism to control the activity of the ClpXP adaptor protein YjbH
Author(s) -
Engman Jakob,
Wachenfeldt Claes
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12842
Subject(s) - signal transducing adaptor protein , proteolysis , biology , protein aggregation , microbiology and biotechnology , signal transduction , biochemistry , proteases , enzyme
Summary Bacteria use stress response pathways to activate diverse target genes to react to a variety of stresses. The B acillus subtilis Spx protein is a global transcriptional regulator that controls expression of more than 140 genes and operons in response to thiol‐specific oxidative stress. Under nonstress conditions the concentration of S px is kept low by proteolysis catalyzed by the ClpXP complex. Spx protein levels increase in response to disulfide stress and decrease when the cells cope with the stress. The cytosolic adaptor protein YjbH is required to target Spx for efficient proteolysis by ClpXP . We demonstrate that YjbH aggregates in response to disulfide stress, that is, the YjbH protein is soluble under nonstressed conditions and destabilized during stress leading to aggregation. Stress conditions (heat and ethanol) that cause severe perturbations in protein stability/folding also induced aggregation of YjbH and led to induction of Spx . By heterologous expression of a less aggregation prone YjbH homolog Spx induction was abolished. Thus we show that moderation of YjbH solubility is an important mechanism of signal transduction and represents a new mechanism of controlling the activity of adaptor proteins.