Evidence for steric regulation of fibrinogen binding to staphylococcus aureus Fibronectin-binding Protein A ( FnBPA)
Author(s)
Type
Journal Article
Abstract
The adjacent fibrinogen (Fg)- and fibronectin (Fn)-binding sites on Fn-binding protein A (FnBPA), a cell surface protein from Staphylococcus aureus, are implicated in the initiation and persistence of infection. FnBPA contains a single Fg-binding site (that also binds elastin) and multiple Fn-binding sites. Here, we solved the structure of the N2N3 domains containing the Fg-binding site of FnBPA in the apo form and in complex with a Fg peptide. The Fg binding mechanism is similar to that of homologous bacterial proteins but without the requirement for “latch” strand residues. We show that the Fg-binding sites and the most N-terminal Fn-binding sites are nonoverlapping but in close proximity. Although Fg and a subdomain of Fn can form a ternary complex on an FnBPA protein construct containing a Fg-binding site and single Fn-binding site, binding of intact Fn appears to inhibit Fg binding, suggesting steric regulation. Given the concentrations of Fn and Fg in the plasma, this mechanism might result in targeting of S. aureus to fibrin-rich thrombi or elastin-rich tissues.
Date Issued
2014-05-02
Date Acceptance
2014-03-01
Citation
Journal of Biological Chemistry, 2014, 289 (18), pp.12842-12851
ISSN
0021-9258
Publisher
American Society for Biochemistry and Molecular Biology
Start Page
12842
End Page
12851
Journal / Book Title
Journal of Biological Chemistry
Volume
289
Issue
18
Copyright Statement
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Unported License applies to Author Choice Articles
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000335581400053&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Fibrinogen
Fibronectin
Isothermal Titration Calorimetry
Staphylococcus aureus
Surface Plasmon Resonance (SPR)
X-ray Crystallography
FnBPA
CLUMPING FACTOR
CRYSTAL-STRUCTURE
GAMMA-CHAIN
AFFINITY
MSCRAMM
SURFACE
DOMAIN
MODEL
VALIDATION
REFINEMENT
Publication Status
Published
Date Publish Online
2014-03-13