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

Journal Article · · Structure

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
Grant/Contract Number:
AI-16892; P41 GM103403; AC02-06CH11357; GM-62580
OSTI ID:
1398095
Alternate ID(s):
OSTI ID: 1328785
Journal Information:
Structure, Journal Name: Structure Vol. 24 Journal Issue: 10; ISSN 0969-2126
Publisher:
ElsevierCopyright Statement
Country of Publication:
United Kingdom
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

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