A bacterium that can cause lethal infections in people appears to attach itself to two proteins in blood that play roles in forming clots and helping wounds heal.
This insight helps explain how the bacterium, Staphylococcus aureus, “co-operates” with two proteins, fibrinogen and fibronectin, to cause a dangerous heart infection.
“Bacteria have evolved various mechanisms to exploit human proteins to cause infection. Understanding these mechanisms might not only lead to the development of new therapeutics but can also provide important information regarding the normal role of these human proteins in the body,” says Jennifer Potts, a biology professor at the University of York.
Potts and colleagues used X-ray crystallography, biophysical techniques, and bacterial assays to investigate the process.
In research published in the Journal of Biological Chemistry, they solved the three dimensional structure of the bacterial protein FnBPA in complex with a small part of the human protein fibrinogen.
This work showed that the fibrinogen binding site on FnBPA is close to, but not overlapping with, the binding site for fibronectin.
They then studied the binding of the two human proteins simultaneously to FnBPA and found that binding of fibronectin appears to block binding of fibrinogen to the bacterial protein. It appears that regulation of binding arises due to the close proximity of the fibrinogen and fibronectin binding sites on the bacterial protein and the large size of the human proteins.
While the research provides the first biophysical evidence in support of the co-operation previously observed in the infection studies, it is still not clear how these two observations are linked. The scientists are planning further studies.
“This study showed how this bacterium interacts with proteins found in our blood, which may give us an insight into how these deadly heart infections occur. This is an important step towards developing new treatments, but more research is needed to fully understand this interaction,” says Potts.
The British Heart Foundation and the Biotechnology and Biological Sciences Research Council supported the project.
Original Article:
《Evidence for Steric Regulation of Fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA)》, Published on Journal 《The Journal of Biological Chemistry》in March 13, 2014.