期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：48
页码：13869-13874
DOI：10.1073/pnas.1608406113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceGram-positive bacteria have evolved to use host fibronectin via molecules called "fibronectin-binding proteins" (FnBPs) to execute their host-interaction functions. The anchorless FnBPs, for which neither structural information nor a well-defined function is available, were recently proposed to be important virulence factors. Our work illustrates the organization of fibronectin/fibrinogen-binding protein from Streptococcus suis (FBPS), a representative member of the anchorless FnBP group from S. suis, by small-angle X-ray scattering and describes two terminal-half structures at high resolution. The C-terminal half of FBPS interacts with fibronectin and the N-terminal half attaches to the bacterial surface. Functionally, FBPS contributes to the bacterial pathogenesis both as an adhesin and as a chemokine stimulator. 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 [IMG]f1.gif" ALT="A" BORDER="0">, 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 {beta}1 integrin receptors to induce chemokine production.
关键词：fibronectin-binding protein of Streptococcus suis ; structure ; novel fold ; fibronectin-binding property ; function
