The Flexible Loop of Staphylococcus aureus IsdG Is Required for Its Degradation in the Absence of Heme
Open accessAbstract
Degradation of specific native proteins allows bacteria to rapidly adapt to changing environments when the activity of those proteins is no longer required. Although these processes are vital to bacterial survival, relatively little is known regarding how bacterial proteins are recognized and targeted for degradation. Staphylococcus aureus is an important human pathogen that requires iron for growth and pathogenesis. In the vertebrate host, S. aureus fulfills its iron requirement by obtaining heme iron from host hemoproteins via IsdG- and IsdI-mediated heme degradation. IsdG and IsdI are structurally and mechanistically analogous but are differentially regulated by iron and heme availability. Specifically, IsdG is targeted for degradation in the absence of heme. Therefore, we utilized the differential regulation of IsdG and IsdI to investigate the mechanism of regulated proteolysis. In contrast to canonical protease recognition sequences, we show that IsdG is targeted for degradation by internally coded sequences. Specifically, a flexible loop near the heme-binding pocket is required for IsdG degradation in the absence of heme.
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IsdG degradation without heme does not proceed through the N-end rule or the SsrA tag, because neither terminus is required for proteolytic recognition.
“The targeted degradation of IsdG in the absence of heme does not occur through either the N-end rule or the SsrA tag as neither termini are required for proteolytic recognition [53].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [53]
An internal sequence in the flexible loop of IsdG is needed for heme-dependent degradation of the protein.
“Recently it was determined that an internal sequence located within the flexible loop region of IsdG is required for the heme-dependent degradation of this protein [53].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [53]
No known staphylococcal protease degrades apo-IsdG, suggesting that S. aureus has an unidentified protease for protein turnover.
“Furthermore, none of the known staphylococcal proteases are responsible for the degradation of apo-IsdG, suggesting that S. aureus encodes an as-yet unidentified protease involved in protein turnover [53].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [53]
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A battle for iron: host sequestration and Staphylococcus aureus acquisition
Haley, K. P., & Skaar, E. P. (2012) · Microbes and Infection · doi:10.1016/j.micinf.2011.11.001 · Cited by 157 · see citing works
“Recently it was determined that an internal sequence located within the flexible loop region of IsdG is required for the heme-dependent degradation of this protein [53].”
BackgroundInfluentialSelf-citationIsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus
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Self-citationRegulation of host hemoglobin binding by the Staphylococcus aureus Clp proteolytic system
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- Authors
- Reniere, M. L., Haley, K. P., & Skaar, E. P.
- Affiliations
- Vanderbilt University Medical Center (US)
- Corresponding author
- Skaar, Eric P.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-07-11
- Volume
- 50
- Issue
- 31
- Pages
- 6730-6737
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC3149779
- OpenAlex
- W2002168715
- Cited by
- 25
- References
- 31
- Citations by year
- 2025: 4 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 3
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007751)
- National Institute of Allergy and Infectious Diseases (AI073843, AI69233, R01AI069233, T32AI007611, R01AI073843)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- Staphylococcus aureus, heme degradation, regulated proteolysis, protein degradation, flexible loop, heme binding pocket, iron acquisition, heme proteins
- MeSH terms
- Bacterial Proteins, Binding Sites, Heme, Hemeproteins, Humans, Mixed Function Oxygenases, Iron, Oxygenases, Protein Conformation, Protein Denaturation, Staphylococcus aureus, Point Mutation, Gene Targeting, Mutant Chimeric Proteins, Protein Stability
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