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HspQ Functions as a Unique Specificity-Enhancing Factor for the AAA+ Lon Protease.

ABSTRACT: The AAA+ Lon protease is conserved from bacteria to humans, performs crucial roles in protein homeostasis, and is implicated in bacterial pathogenesis and human disease. We investigated how Lon selectively degrades specific substrates among a diverse array of potential targets. We report the discovery of HspQ as a new Lon substrate, unique specificity-enhancing factor, and potent allosteric activator. Lon recognizes HspQ via a C-terminal degron, whose precise presentation, in synergy with multipartite contacts with the native core of HspQ, is required for allosteric Lon activation. Productive HspQ-Lon engagement enhances degradation of multiple new and known Lon substrates. Our studies reveal the existence and simultaneous utilization of two distinct substrate recognition sites on Lon, an HspQ binding site and an HspQ-modulated allosteric site. Our investigations unveil an unprecedented regulatory use of an evolutionarily conserved heat shock protein and present a distinctive mechanism for how Lon protease achieves temporally enhanced substrate selectivity.

SUBMITTER: Puri N

PROVIDER: S-EPMC8054221 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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HspQ Functions as a Unique Specificity-Enhancing Factor for the AAA+ Lon Protease.

Puri Neha N Karzai A Wali AW

Molecular cell 20170601 5

The AAA+ Lon protease is conserved from bacteria to humans, performs crucial roles in protein homeostasis, and is implicated in bacterial pathogenesis and human disease. We investigated how Lon selectively degrades specific substrates among a diverse array of potential targets. We report the discovery of HspQ as a new Lon substrate, unique specificity-enhancing factor, and potent allosteric activator. Lon recognizes HspQ via a C-terminal degron, whose precise presentation, in synergy with multip ...[more]

PMID: 28575662

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Project description:Acinetobacter baumannii is a Gram-negative opportunistic pathogen that is known to survive harsh environmental conditions and is a leading cause of hospital-acquired infections. Specifically, multicellular communities (known as biofilms) of A. baumannii can withstand desiccation and survive on hospital surfaces and equipment. Biofilms are bacteria embedded in a self-produced extracellular matrix composed of proteins, sugars, and/or DNA. Bacteria in a biofilm are protected from environmental stresses, including antibiotics, which provides the bacteria with selective advantage for survival. Although some gene products are known to play roles in this developmental process in A. baumannii, mechanisms and signaling remain mostly unknown. Here, we find that Lon protease in A. baumannii affects biofilm development and has other important physiological roles, including motility and the cell envelope. Lon proteases are found in all domains of life, participating in regulatory processes and maintaining cellular homeostasis. These data reveal the importance of Lon protease in influencing key A. baumannii processes to survive stress and to maintain viability.IMPORTANCE Acinetobacter baumannii is an opportunistic pathogen and is a leading cause of hospital-acquired infections. A. baumannii is difficult to eradicate and to manage, because this bacterium is known to robustly survive desiccation and to quickly gain antibiotic resistance. We sought to investigate biofilm formation in A. baumannii, since much remains unknown about biofilm formation in this bacterium. Biofilms, which are multicellular communities of bacteria, are surface attached and difficult to eliminate from hospital equipment and implanted devices. Our research identifies multifaceted physiological roles for the conserved bacterial protease Lon in A. baumannii These roles include biofilm formation, motility, and viability. This work broadly affects and expands understanding of the biology of A. baumannii, which will permit us to find effective ways to eliminate the bacterium.

Dataset Information

HspQ Functions as a Unique Specificity-Enhancing Factor for the AAA+ Lon Protease.

Publications

HspQ Functions as a Unique Specificity-Enhancing Factor for the AAA+ Lon Protease.

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