Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins.
Cells use molecular chaperones and proteases to implement the essential quality control mechanism of proteins. The DegP (HtrA) protein, essential for the survival of Escherichia coli cells at elevated temperatures with homologues found in almost all organisms uniquely has both functions. Here we report a mechanism for DegP to activate both functions via formation of large cage-like 12- and 24-mers after binding to substrate proteins. Cryo-electron microscopic and biochemical studies revealed that both oligomers are consistently assembled by blocks of DegP trimers, via pairwise PDZ1-PDZ2 interactions between neighboring trimers. Such interactions simultaneously eliminate the inhibitory effects of the PDZ2 domain. Additionally, both DegP oligomers were also observed in extracts of E. coli cells, strongly implicating their physiological importance.
Jiang
Jiansen
J
Department of Biological Sciences and Biotechnology, State-Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Zhang
Xuefeng
X
Chen
Yong
Y
Wu
Yi
Y
Zhou
Z Hong
ZH
Chang
Zengyi
Z
Sui
Sen-Fang
SF
D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013379:Substrate Specificity
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; C061682:DegP protease; D012697:Serine Endopeptidases; C054542:chymostatin-sensitive angiotensin II-generating enzyme