Peptidic small molecule activators of the stress sensor DegS.
Bacterial DegS is a regulatory protease that acts as a molecular stress sensor and initiates a periplasmic stress response pathway. Upon binding of misfolded proteins to its PDZ domain, the protease domain of DegS is allosterically activated, thereby initiating a signal cascade that results in the elevated expression of protein quality control factors. Although the structural basis of this activation mode has been elucidated previously, it is not yet fully understood if binding to the PDZ domain is sufficient for protease domain activation or if secondary interactions with the protease domain are required. Here, we demonstrate that tripeptidic small molecule activators which only bind to the PDZ domain are sufficient to trigger DegS activation. Furthermore, we show that the hydrophobicity of the peptidic small molecule activators is a critical determinant for efficient activation.
Hauske
Patrick
P
Chemical Genomics Centre der Max-Planck-Gesellschaft, Otto-Hahn-Str. 15, 44227 Dortmund, Germany.
Mamant
Nicolette
N
Hasenbein
Sonja
S
Nickel
Sabrina
S
Ottmann
Christian
C
Clausen
Tim
T
Ehrmann
Michael
M
Kaiser
Markus
M
D000495:Allosteric Site; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D054731:PDZ Domains; D010649:Phenylalanine / Q000737:chemistry; D017510:Protein Folding; D013312:Stress, Physiological / Q000502:physiology
D001426:Bacterial Proteins; C066496:DegS protein, Bacteria; D009842:Oligopeptides; D010649:Phenylalanine