Structural and functional analysis of an anchorless fibronectin-binding protein FBPS from Gram-positive bacterium Streptococcus suis.
The anchorless fibronectin-binding proteins (FnBPs) are a group of important virulence factors for which the structures are not available and the functions are not well defined. In this study we performed comprehensive studies on a prototypic member of this group: the fibronectin-/fibrinogen-binding protein from Streptococcus suis (FBPS). The structures of the N- and C-terminal halves (FBPS-N and FBPS-C), which together cover the full-length protein in sequence, were solved at a resolution of 2.1 and 2.6 Å, respectively, and each was found to be composed of two domains with unique folds. Furthermore, we have elucidated the organization of these domains by small-angle X-ray scattering. We further showed that the fibronectin-binding site is located in FBPS-C and that FBPS promotes the adherence of S suis to host cells by attaching the bacteria via FBPS-N. Finally, we demonstrated that FBPS functions both as an adhesin, promoting S suis attachment to host cells, and as a bacterial factor, activating signaling pathways via β1 integrin receptors to induce chemokine production.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
Abednego Moki
AM
Musyoki
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
Zhongyu
Z
Shi
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
Chunling
C
Xuan
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.|Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
Guangwen
G
Lu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Jianxun
J
Qi
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Feng
F
Gao
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Beiwen
B
Zheng
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Qiangmin
Q
Zhang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Yan
Y
Li
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
Joel
J
Haywood
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Cuihua
C
Liu
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Jinghua
J
Yan
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Yi
Y
Shi
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; gaof@im.ac.cn.|University of the Chinese Academy of Sciences, Beijing 100049, China.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
George F
GF
Gao
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013290:Streptococcal Infections / Q000235:genetics* / Q000382:microbiology; D017011:Streptococcus suis / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics
D018829:Adhesins, Bacterial; D005353:Fibronectins; D037521:Virulence Factors; C078635:fibronectin-binding proteins, bacterial
fibronectin-binding property; fibronectin-binding protein of Streptococcus suis; function; novel fold; structure