title: 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.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China, Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China, Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Pian
authors.affiliation: Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and.
authors.forename: Jingpeng
authors.initials: J
authors.lastname: Ge
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
authors.forename: Huaijie
authors.initials: H
authors.lastname: Hao
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China, miniminiyuan@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China, jiangyq@nic.bmi.ac.cn.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, and maojunyang@tsinghua.edu.cn.
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010587:Phagocytosis; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology; D017011:Streptococcus suis / Q000201:enzymology*; D034421:Sus scrofa; D011503:Transglutaminases / Q000737:chemistry* / Q000502:physiology; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D011503:Transglutaminases
keywords: SsTGase; antiphagocytosis; crystal structure; homodimer; microbial pathogenesis; microbiology; transglutaminase; virulence factor