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The I domain of the AAA+ HslUV protease coordinates substrate binding, ATP hydrolysis, and protein degradation.

ABSTRACT: In the AAA+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. Here, we show that the N-terminal residues of an Arc substrate initially bind in the HslU axial pore, with key contacts mediated by a pore loop that is highly conserved in all AAA+ unfoldases. Disordered loops from the six intermediate domains of the HslU hexamer project into a funnel-shaped cavity above the pore and are positioned to contact protein substrates. Mutations in these I-domain loops increase K(M) and decrease V(max) for degradation, increase the mobility of bound substrates, and prevent substrate stimulation of ATP hydrolysis. HslU-?I has negligible ATPase activity. Thus, the I domain plays an active role in coordinating substrate binding, ATP hydrolysis, and protein degradation by the HslUV proteolytic machine.

SUBMITTER: Sundar S

PROVIDER: S-EPMC3324763 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The I domain of the AAA+ HslUV protease coordinates substrate binding, ATP hydrolysis, and protein degradation.

Sundar Shankar S Baker Tania A TA Sauer Robert T RT

Protein science : a publication of the Protein Society 20120104 2

In the AAA+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. Here, we show that the N-terminal residues of an Arc substrate initially bind in the HslU axial pore, with key contacts mediated by a pore loop that is highly conserved in all AAA+ unfoldases. Disordered loops from the six intermediate domains of the HslU hexamer project into a funnel-shaped cavity above the pore and are positi ...[more]

PMID: 22102327

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