The Anti-Aggregation Holdase Hsp33 Promotes the Formation of Folded Protein Structures

Moayed, Fatemeh; Bezrukavnikov, Sergey; Naqvi, Mohsin M.; Groitl, Bastian; Cremers, Claudia M.; Ghosh, Kingshuk; Jakob, Ursula; Tans, Sander J.

doi:10.1016/j.bpj.2019.10.040

Cited by 18 publications

(12 citation statements)

References 40 publications

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“…DnaK/J may bind to HtpG to reactivate inactive protein substrates on the path to native protein fold ( 93 ). The holdase HslO binds to unfolded protein, which is released to DnaK for folding ( 94 ). GrpE may interact with DnaK, thereby dissociating ADP and releasing the bound protein ( 95 ).…”

Section: Resultsmentioning

confidence: 99%

Proteomic and Transcriptomic Analysis of Microviridae φX174 Infection Reveals Broad Upregulation of Host Escherichia coli Membrane Damage and Heat Shock Responses

et al. 2021

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Measuring host-bacteriophage dynamics is an important approach to understanding bacterial survival functions and responses to infection. The model Microviridae bacteriophage φX174 is endemic to the human gut and has been studied for over 70 years, but the host response to infection has never been investigated in detail. To address this gap in our understanding of this important interaction within our microbiome, we have measured host Escherichia coli C proteomic and transcriptomic response to φX174 infection. We used mass spectrometry and RNA sequencing (RNA-seq) to identify and quantify all 11 φX174 proteins and over 1,700 E. coli proteins, enabling us to comprehensively map host pathways involved in φX174 infection. Most notably, we see significant host responses centered on membrane damage and remodeling, cellular chaperone and translocon activity, and lipoprotein processing, which we speculate is due to the peptidoglycan-disruptive effects of the φX174 lysis protein E on MraY activity. We also observe the massive upregulation of small heat shock proteins IbpA/B, along with other heat shock pathway chaperones, and speculate on how the specific characteristics of holdase protein activity may be beneficial for viral infections. Together, this study enables us to begin to understand the proteomic and transcriptomic host responses of E. coli to Microviridae infections and contributes insights to the activities of this important model host-phage interaction. IMPORTANCE A major part of the healthy human gut microbiome is the Microviridae bacteriophage, exemplified by the model φX174 phage, and their E. coli hosts. Although much has been learned from studying φX174 over the last half-century, until this work, the E. coli host response to infection has never been investigated in detail. We reveal the proteomic and transcriptomic pathways differentially regulated during the φX174 infection cycle and uncover the details of a coordinated cellular response to membrane damage that results in increased lipoprotein processing and membrane trafficking, likely due to the phage antibiotic-like lysis protein. We also reveal that small heat shock proteins IbpA/B are massively upregulated during infection and that these holdase chaperones are highly conserved across the domains of life, indicating that reliance on them is likely widespread across viruses.

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Section: Resultsmentioning

confidence: 99%

Proteomic and Transcriptomic Analysis of Microviridae φX174 Infection Reveals Broad Upregulation of Host Escherichia coli Membrane Damage and Heat Shock Responses

et al. 2021

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“…Eukaryotic Hsp90, for example, and its cochaperones play a critical role in the conformational maturation of specific clients such as protein kinases, stabilizing metastable states that are poorly populated in the absence of these chaperones [100]. Furthermore, ATP‐independent chaperones such as small heat shock proteins, trigger factor, and Spy (in the bacterial periplasm) have been shown to modulate protein folding pathways, although whether and how these chaperones accelerate the folding of endogenous substrates is at present unclear [101–103]. Finally, it will be important to recapitulate the full complexity of folding in vivo , by studying chaperone action also in the context of translation.…”

Section: Discussionmentioning

confidence: 99%

Recent advances in understanding catalysis of protein folding by molecular chaperones

2020

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Molecular chaperones are highly conserved proteins that promote proper folding of other proteins in vivo. Diverse chaperone systems assist de novo protein folding and trafficking, the assembly of oligomeric complexes, and recovery from stress‐induced unfolding. A fundamental function of molecular chaperones is to inhibit unproductive protein interactions by recognizing and protecting hydrophobic surfaces that are exposed during folding or following proteotoxic stress. Beyond this basic principle, it is now clear that chaperones can also actively and specifically accelerate folding reactions in an ATP‐dependent manner. We focus on the bacterial Hsp70 and chaperonin systems as paradigms, and review recent work that has advanced our understanding of how these chaperones act as catalysts of protein folding.

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“…The unfolded, hydrophilic linker region binds to unfolded client proteins via electrostatic interaction (51, 53). This effect is further stabilized through hydrophobic interactions between the client and the well-folded N-terminal domain of Hsp33 (53). Additional activators of Hsp33's chaperone function have been identified over the years, including reactive bromine species (e.g., HOBr) (24), a combination of peroxide stress and heat stress (41,48), bile salts (54), and, as recently noted, atmospheric-pressure plasma (55).…”

Section: Cellular Defenses Against Hocl Stress: Rapid Activation Of Chaperone Holdases Helps Hocl-stressed Cells Cope With Hocl-induced Pmentioning

confidence: 98%

“…Once reducing conditions are restored, oxidized Hsp33 dimers are converted to reduced Hsp33 dimers, which are still bound to their client proteins, likely until ATP-dependent foldase systems such as the DnaK/ DnaJ/GrpE systems are fully functional for subsequent refolding of the client proteins. However, a recent study suggested that Hsp33 may be involved in the process of refolding of their client proteins (53).…”

Section: Cellular Defenses Against Hocl Stress: Rapid Activation Of Chaperone Holdases Helps Hocl-stressed Cells Cope With Hocl-induced Pmentioning

confidence: 99%

Bacterial Defense Systems against the Neutrophilic Oxidant Hypochlorous Acid

2020

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Neutrophils kill invading microbes and therefore represent the first line of defense of the innate immune response. Activated neutrophils assemble NADPH oxidase to convert substantial amounts of molecular oxygen into superoxide, which, after dismutation into peroxide, serves as the substrate for the generation of the potent antimicrobial hypochlorous acid (HOCl) in the phagosomal space. In this minireview, we explore the most recent insights into physiological consequences of HOCl stress. Not surprisingly, Gram-negative bacteria have evolved diverse posttranslational defense mechanisms to protect their proteins, the main targets of HOCl, from HOCl-mediated damage. We discuss the idea that oxidation of conserved cysteine residues and partial unfolding of its structure convert the heat shock protein Hsp33 into a highly active chaperone holdase that binds unfolded proteins and prevents their aggregation. We examine two novel members of the Escherichia coli chaperone holdase family, RidA and CnoX, whose thiol-independent activation mechanism differs from that of Hsp33 and requires N-chlorination of positively charged amino acids during HOCl exposure. Furthermore, we summarize the latest findings with respect to another bacterial defense strategy employed in response to HOCl stress, which involves the accumulation of the universally conserved biopolymer inorganic polyphosphate. We then discuss sophisticated adaptive strategies that bacteria have developed to enhance their survival during HOCl stress. Understanding bacterial defense and survival strategies against one of the most powerful neutrophilic oxidants may provide novel insights into treatment options that potentially compromise the ability of pathogens to resist HOCl stress and therefore may increase the efficacy of the innate immune response.

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The Anti-Aggregation Holdase Hsp33 Promotes the Formation of Folded Protein Structures

Cited by 18 publications

References 40 publications

Proteomic and Transcriptomic Analysis of Microviridae φX174 Infection Reveals Broad Upregulation of Host Escherichia coli Membrane Damage and Heat Shock Responses

Proteomic and Transcriptomic Analysis of Microviridae φX174 Infection Reveals Broad Upregulation of Host Escherichia coli Membrane Damage and Heat Shock Responses

Recent advances in understanding catalysis of protein folding by molecular chaperones

Bacterial Defense Systems against the Neutrophilic Oxidant Hypochlorous Acid

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