A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis

Baytshtok, Vladimir; Fei, Xue; Grant, Robert A.; Baker, Tania A.; Sauer, Robert T.

doi:10.1016/j.str.2016.08.012

A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis

Journal Article · Thu Sep 22 00:00:00 EDT 2016 · Structure

DOI:https://doi.org/10.1016/j.str.2016.08.012· OSTI ID:1398095

Baytshtok, Vladimir; Fei, Xue; Grant, Robert A.; Baker, Tania A.; Sauer, Robert T.

The I domain of HslU sits above the AAA+ ring and forms a funnel-like entry to the axial pore, where protein substrates are engaged, unfolded, and translocated into HslV for degradation. The L199Q I-domain substitution, which was originally reported as a loss-of-function mutation, resides in a segment that appears to adopt multiple conformations as electron density is not observed in HslU and HslUV crystal structures. The L199Q sequence change does not alter the structure of the AAA+ ring or its interactions with HslV but increases I-domain susceptibility to limited endoproteolysis. Notably, the L199Q mutation increases the rate of ATP hydrolysis substantially, results in slower degradation of some proteins but faster degradation of other substrates, and markedly changes the preference of HslUV for initiating degradation at the N or C terminus of model substrates. As such, a structurally dynamic region of the I domain plays a key role in controlling protein degradation by HslUV.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1398095

Alternate ID(s):: OSTI ID: 1328785

Journal Information:: Structure, Journal Name: Structure Journal Issue: 10 Vol. 24; ISSN 0969-2126

Publisher:: ElsevierCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis

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