4b60

Structural highlights

Disease

[FIBG_HUMAN] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.

Function

[FNBA_STAA8] Possesses multiple, substituting fibronectin (Fn) binding regions, each capable of conferring adherence to both soluble and immobilized forms of Fn. This confers to S.aureus the ability to invade endothelial cells both in vivo and in vitro, without requiring additional factors, although in a slow and inefficient way through actin rearrangements in host cells. This invasion process is mediated by integrin alpha-5/beta-1. Promotes bacterial attachment to both soluble and immobilized forms of fibrinogen (Fg) by means of a unique binding site localized within the 17 C-terminal residues of the gamma-chain of human Fg. Both plasma proteins (Fn and Fg) function as a bridge between bacterium and host cell. Promotes attachment to immobilized elastin peptides in a dose-dependent and saturable manner. Promotes attachment to both full-length and segments of immobilized human tropoelastin at multiple sites in a dose and pH-dependent manner. Promotes adherence to and aggregation of activated platelets independently of other S.aureus surface molecules. Is a critical mediator implicated in the induction of experimental endocarditis in rats with catheter-induced aortic vegetations, promoting both colonization and persistence of the bacterium into the host.^{[1] [2] [3] [4] [5] [6] [7] [8]} [FIBG_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.

References

1. ↑ Signas C, Raucci G, Jonsson K, Lindgren PE, Anantharamaiah GM, Hook M, Lindberg M. Nucleotide sequence of the gene for a fibronectin-binding protein from Staphylococcus aureus: use of this peptide sequence in the synthesis of biologically active peptides. Proc Natl Acad Sci U S A. 1989 Jan;86(2):699-703. PMID:2521391
2. ↑ Wann ER, Gurusiddappa S, Hook M. The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen. J Biol Chem. 2000 May 5;275(18):13863-71. PMID:10788510
3. ↑ Massey RC, Kantzanou MN, Fowler T, Day NP, Schofield K, Wann ER, Berendt AR, Hook M, Peacock SJ. Fibronectin-binding protein A of Staphylococcus aureus has multiple, substituting, binding regions that mediate adherence to fibronectin and invasion of endothelial cells. Cell Microbiol. 2001 Dec;3(12):839-51. PMID:11736995
4. ↑ Que YA, Francois P, Haefliger JA, Entenza JM, Vaudaux P, Moreillon P. Reassessing the role of Staphylococcus aureus clumping factor and fibronectin-binding protein by expression in Lactococcus lactis. Infect Immun. 2001 Oct;69(10):6296-302. PMID:11553573 doi:10.1128/IAI.69.10.6296-6302.2001
5. ↑ Roche FM, Downer R, Keane F, Speziale P, Park PW, Foster TJ. The N-terminal A domain of fibronectin-binding proteins A and B promotes adhesion of Staphylococcus aureus to elastin. J Biol Chem. 2004 Sep 10;279(37):38433-40. Epub 2004 Jul 2. PMID:15234962 doi:10.1074/jbc.M402122200
6. ↑ Heilmann C, Niemann S, Sinha B, Herrmann M, Kehrel BE, Peters G. Staphylococcus aureus fibronectin-binding protein (FnBP)-mediated adherence to platelets, and aggregation of platelets induced by FnBPA but not by FnBPB. J Infect Dis. 2004 Jul 15;190(2):321-9. Epub 2004 Jun 21. PMID:15216468 doi:10.1086/421914
7. ↑ Que YA, Haefliger JA, Piroth L, Francois P, Widmer E, Entenza JM, Sinha B, Herrmann M, Francioli P, Vaudaux P, Moreillon P. Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis. J Exp Med. 2005 May 16;201(10):1627-35. PMID:15897276 doi:jem.20050125
8. ↑ Keane FM, Clarke AW, Foster TJ, Weiss AS. The N-terminal A domain of Staphylococcus aureus fibronectin-binding protein A binds to tropoelastin. Biochemistry. 2007 Jun 19;46(24):7226-32. Epub 2007 May 22. PMID:17516661 doi:10.1021/bi700454x
9. ↑ Stemberk V, Jones RP, Moroz O, Atkin KE, Edwards AM, Turkenburg JP, Leech AP, Massey RC, Potts JR. Evidence for Steric Regulation of Fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA). J Biol Chem. 2014 Mar 13. PMID:24627488 doi:http://dx.doi.org/10.1074/jbc.M113.543546