Functional and Structural Properties of a Novel Protein and Virulence Factor (Protein sHIP) in Streptococcus pyogenes

Wiśniewska, M.; Happonen, Lotta; Kahn, Fredrik; Varjosalo, Markku; Malmström, Lars; Rosenberger, George; Karlsson, Christofer; Cazzamali, Giuseppe; Pozdnyakova, Irina; Frick, Inga-Maria; Björck, Lars; Streicher, Werner; Malmström, Johan; Wikström, Mats

doi:10.1074/jbc.m114.565978

Cited by 7 publications

(18 citation statements)

References 79 publications

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“…Interestingly, this survival rate could be restored to wild-type levels, once HRG was reconstituted into the plasma of HRG -/- mice [63]. These models represent a strong case of what occurs in vivo, and supports the argument that HRG can prevent the growth and spread of S. pyogenes at the site of infection where the environmental milieu favors HRG antibacterial properties [63,70]. …”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 83%

“…An example of invading pathogens having to counter the HRR antibacterial properties was observed by Streicher et al [70], with the discovery of a virulence factor secreted from the AP1 strain of Streptococcus pyogenes ( S. pyogenes ) [70]. This virulence factor was titled streptococcal histidine-rich glycoprotein interaction protein (sHIP) (UniProtKB ID Q99XU0), due to its capacity to specifically target HRG and block the activities of the HRR.…”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

“…In addition, peptides derived from the HRR (GHHPH-like motif) were also ineffective in attenuating growth of S. pyogenes in medium, which demonstrates that even if peptides derived from the HRR can be proteolytically generated and released from the parent protein, the S. pyogenes will still thrive. Interestingly, sHIP ability to bind and act as a soluble decoy receptor for HRG remained constant even under acidic conditions [70]. …”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

“…The ability of sHIP to counter somewhat both the acidic environment and antimicrobial peptides through secretion of the sHIP virulence factor, may explain why the AP1 strain is more pathogenic compared to the less virulent SF370 strain of S. pyogenes [70]. It is worth noting that HRG activity in the presence of Zn 2+ was not directly studied and therefore may play an important role [70].…”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

“…It is worth noting that HRG activity in the presence of Zn 2+ was not directly studied and therefore may play an important role [70]. …”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

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Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

et al. 2017

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Divalent metal ions are essential nutrients for all living organisms and are commonly protein-bound where they perform important roles in protein structure and function. This regulatory control from metals is observed in the relatively abundant plasma protein histidine-rich glycoprotein (HRG), which displays preferential binding to the second most abundant transition element in human systems, Zinc (Zn2+). HRG has been proposed to interact with a large number of protein ligands and has been implicated in the regulation of various physiological and pathological processes including the formation of immune complexes, apoptotic/necrotic and pathogen clearance, cell adhesion, antimicrobial activity, angiogenesis, coagulation and fibrinolysis. Interestingly, these processes are often associated with sites of tissue injury or tumour growth, where the concentration and distribution of Zn2+ is known to vary. Changes in Zn2+ levels have been shown to modify HRG function by altering its affinity for certain ligands and/or providing protection against proteolytic disassembly by serine proteases. This review focuses on the molecular interplay between HRG and Zn2+, and how Zn2+ binding modifies HRG-ligand interactions to regulate function in different settings of tissue injury.

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Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 83%

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

“…It is worth noting that HRG activity in the presence of Zn 2+ was not directly studied and therefore may play an important role [70]. …”

Section: The Antibacterial and Antifungal Properties Of Hrg At Sitmentioning

confidence: 99%

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Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

et al. 2017

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Quantification of Adaptive Immune Responses Against Protein-Binding Interfaces in the Streptococcal M1 Protein

Torres-Sangiao,

Happonen,

Heusel

et al. 2024

Molecular & Cellular Proteomics

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A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies

et al. 2019

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A fundamental challenge in medical microbiology is to characterize the dynamic protein–protein interaction networks formed at the host–pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes , and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and different S. pyogenes serotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis of S. pyogenes cells are localized. The interaction map confirms several previously described protein–protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host–pathogen interactions involving other bacterial species.

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Functional and Structural Properties of a Novel Protein and Virulence Factor (Protein sHIP) in Streptococcus pyogenes

Cited by 7 publications

References 79 publications

Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

Functional Regulation of the Plasma Protein Histidine-Rich Glycoprotein by Zn2+ in Settings of Tissue Injury

Quantification of Adaptive Immune Responses Against Protein-Binding Interfaces in the Streptococcal M1 Protein

A quantitative Streptococcus pyogenes–human protein–protein interaction map reveals localization of opsonizing antibodies

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