Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes
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Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes. / Wisniewska, Magdalena; 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.
In: The Journal of Biological Chemistry, Vol. 289, 13.05.2014, p. 18175-18188.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Functional and Structural Properties of a Novel Protein and Virulence Factor (sHIP) in Streptococcus pyogenes
AU - Wisniewska, Magdalena
AU - Happonen, Lotta
AU - Kahn, Fredrik
AU - Varjosalo, Markku
AU - Malmström, Lars
AU - Rosenberger, George
AU - Karlsson, Christofer
AU - Cazzamali, Giuseppe
AU - Pozdnyakova, Irina
AU - Frick, Inga-Maria
AU - Björck, Lars
AU - Streicher, Werner
AU - Malmström, Johan
AU - Wikström, Mats
N1 - Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
PY - 2014/5/13
Y1 - 2014/5/13
N2 - Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.
AB - Streptococcus pyogenes is a significant bacterial pathogen in the human population. The importance of virulence factors for the survival and colonization of S. pyogenes is well established, and many of these factors are exposed to the extracellular environment enabling bacterial interactions with the host. In the present study we quantitatively analyzed and compared S. pyogenes proteins in the growth medium of a strain that is virulent to mice, with a non-virulent strain. Particularly one of these proteins was present at significantly higher levels in stationary growth medium from the virulent strain. We determined the three-dimensional structure of the protein that showed a unique tetrameric organization composed of four helix-loop-helix motifs. Affinity pull-down mass spectrometry analysis in human plasma demonstrated that the protein interacts with histidine-rich glycoprotein (HRG), and the name sHIP (streptococcal Histidine-rich glycoprotein Interacting Protein) is therefore proposed. HRG has antibacterial activity, and when challenged by HRG, sHIP was found to rescue S. pyogenes bacteria. This and the finding that patients with invasive S. pyogenes infection respond with antibody production against sHIP, suggest a role for the protein in S. pyogenes pathogenesis.
U2 - 10.1074/jbc.M114.565978
DO - 10.1074/jbc.M114.565978
M3 - Journal article
C2 - 24825900
VL - 289
SP - 18175
EP - 18188
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
ER -
ID: 117862869