Functional and Structural Characterization of the Antiphagocytic Properties of a Novel Transglutaminase from Streptococcus suis.

Abstract

Streptococcus suis serotype 2 (Ss2) is an important swine and human zoonotic pathogen. In the present study, we identified a novel secreted immunogenic protein, SsTGase, containing a highly conserved eukaryotic-like transglutaminase (TGase) domain at the N terminus. We found that inactivation of SsTGase significantly reduced the virulence of Ss2 in a pig infection model and impaired its antiphagocytosis in human blood. We further solved the crystal structure of the N-terminal portion of the protein in homodimer form at 2.1 Å. Structure-based mutagenesis and biochemical studies suggested that disruption of the homodimer directly resulted in the loss of its TGase activity and antiphagocytic ability. Characterization of SsTGase as a novel virulence factor of Ss2 by acting as a TGase would be beneficial for developing new therapeutic agents against Ss2 infections.

• Authors: Jie Yu, Yaya Pian, Jingpeng Ge, Jie Guo, Yuling Zheng, Hua Jiang, Huaijie Hao, Yuan Yuan, Yongqiang Jiang, Maojun Yang
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 31 Pg. 19081-92 (Jul 31 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26085092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Bacterial Proteins
• Virulence Factors
• Transglutaminases

Topics

• Amino Acid Sequence
• Animals
• Bacterial Proteins (chemistry, physiology)
• Catalytic Domain
• Conserved Sequence
• Crystallography, X-Ray
• Models, Molecular
• Molecular Sequence Data
• Phagocytosis
• Protein Multimerization
• Protein Structure, Quaternary
• Protein Structure, Secondary
• Streptococcal Infections (immunology, microbiology)
• Streptococcus suis (enzymology)
• Sus scrofa
• Transglutaminases (chemistry, physiology)
• Virulence Factors