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

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

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)18175-18188
JournalJournal of Biological Chemistry
Issue number26
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Infectious Medicine


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