The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies

Robert Wrase, Hannah Scott, Rolf Hilgenfeld*, Guido Hansen

*Korrespondierende/r Autor/-in für diese Arbeit
26 Zitate (Scopus)

Abstract

Proteases of the HtrA family are key factors dealing with folding stress in the periplasmatic compartment of prokaryotes. In Escherichia coli, the well-characterized HtrA family members DegS and DegP counteract the accumulation of unfolded outer-membrane proteins under stress conditions. Whereas DegS serves as a folding-stress sensor, DegP is a chaperone-protease facilitating refolding or degradation of defective outer-membrane proteins. Here, we report the 2.15-Å-resolution crystal structure of the second major chaperone-protease of the periplasm, DegQ from Legionella fallonii. DegQ assembles into large, cage-like 12-mers that form independently of unfolded substrate proteins. We provide evidence that 12-mer formation is essential for the degradation of substrate proteins but not for the chaperone activity of DegQ. In the current model for the regulation of periplasmatic chaperone-proteases, 6-meric assemblies represent important proteaseresting states. However, DegQ is unable to form such 6-mers, suggesting divergent regulatory mechanisms for DegQ and DegP. To understand how the protease activity of DegQ is controlled, we probed its functional properties employing designed protein variants. Combining crystallographic, biochemical, and mutagenic data, we present a mechanistic model that suggests how protease activity of DegQ 12-mers is intrinsically regulated and how deleterious proteolysis by free DegQ 3-mers is prevented. Our study sheds light on a previously uncharacterized component of the prokaryotic stress-response system with implications for other members of the HtrA family.

OriginalspracheEnglisch
ZeitschriftProceedings of the National Academy of Sciences of the United States of America
Jahrgang108
Ausgabenummer26
Seiten (von - bis)10490-10495
Seitenumfang6
ISSN0027-8424
DOIs
PublikationsstatusVeröffentlicht - 28.06.2011

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