Fibrinogen activates the capture of human plasminogen by staphylococcal fibronectin-binding proteins
Citation:
Herman-Bausier, P. and Pietrocola, G. and Foster, T.J. and Speziale, P. and Dufr??ne, Y.F., Fibrinogen activates the capture of human plasminogen by staphylococcal fibronectin-binding proteins, mBio, 8, 5, 2017, e01067-17Download Item:
Abstract:
Invasive bacterial pathogens can capture host plasminogen (Plg) and al-
low it to form plasmin. This process is of medical importance as surface-bound plas-
min promotes bacterial spread by cleaving tissue components and favors immune
evasion by degrading opsonins. In
Staphylococcus aureus
, Plg binding is in part
mediated by cell surface fibronectin-binding proteins (FnBPs), but the underlying
molecular mechanism is not known. Here, we use single-cell and single-molecule
techniques to demonstrate that FnBPs capture Plg by a sophisticated
activation
mechanism involving fibrinogen (Fg), another ligand found in the blood. We show
that while FnBPs bind to Plg through weak (
200-pN) molecular bonds, direct inter-
action of the adhesins with Fg through the high-affinity dock, lock, and latch mech-
anism dramatically increases the strength of the FnBP-Plg bond (up to
2,000 pN).
Our results point to a new model in which the binding of Fg triggers major confor-
mational changes in the FnBP protein, resulting in the buried Plg-binding domains
being projected and exposed away from the cell surface, thereby promoting strong
interactions with Plg. This study demonstrated a previously unidentified role for a
ligand-binding interaction by a staphylococcal cell surface protein, i.e., changing the
protein orientation to activate a cryptic biological function
Author's Homepage:
http://people.tcd.ie/tfoster
Author: FOSTER, TIMOTHY
Type of material:
Journal ArticleCollections
Series/Report no:
mBio8
5
Availability:
Full text availableDOI:
http://dx.doi.org/10.1128/mBio.01067-17Metadata
Show full item recordLicences: