4b5z

From Proteopedia

(Difference between revisions)

Current revision

Structure of the apo-rFnBPA(189-505) from Staphylococcus aureus

Structural highlights

4b5z is a 1 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

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- and the most N-terminal Fn-binding sites are non-overlapping but in close proximity. While Fg and a sub-domain of Fn can form a ternary complex on an FnBPA protein construct containing a Fg- 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.

Evidence for Steric Regulation of Fibrinogen binding to Staphylococcus aureus fibronectin-binding protein A (FnBPA).,Stemberk V, Jones RP, Moroz O, Atkin KE, Edwards AM, Turkenburg JP, Leech AP, Massey RC, Potts JR J Biol Chem. 2014 Mar 13. PMID:24627488^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b5z"

@@ Line 3: / Line 3: @@
 <StructureSection load='4b5z' size='340' side='right'caption='[[4b5z]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b5z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staa8 Staa8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B5Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b5z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B5Z FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4b60|4b60]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b5z OCA], [https://pdbe.org/4b5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b5z RCSB], [https://www.ebi.ac.uk/pdbsum/4b5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b5z ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/FNBA_STAA8 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.<ref>PMID:2521391</ref> <ref>PMID:10788510</ref> <ref>PMID:11736995</ref> <ref>PMID:11553573</ref> <ref>PMID:15234962</ref> <ref>PMID:15216468</ref> <ref>PMID:15897276</ref> <ref>PMID:17516661</ref>
+[https://www.uniprot.org/uniprot/FNBA_STAA8 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.<ref>PMID:2521391</ref> <ref>PMID:10788510</ref> <ref>PMID:11736995</ref> <ref>PMID:11553573</ref> <ref>PMID:15234962</ref> <ref>PMID:15216468</ref> <ref>PMID:15897276</ref> <ref>PMID:17516661</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Staa8]]
+[[Category: Staphylococcus aureus subsp. aureus NCTC 8325]]
-[[Category: Atkin, K E]]
+[[Category: Atkin KE]]
-[[Category: Moroz, O]]
+[[Category: Moroz O]]
-[[Category: Potts, J R]]
+[[Category: Potts JR]]
-[[Category: Stemberk, V]]
+[[Category: Stemberk V]]
-[[Category: Turkenburg, J P]]
+[[Category: Turkenburg JP]]
-[[Category: Cell adhesion]]
-[[Category: Fibrinogen binding]]

4b5z

From Proteopedia

Current revision

Structure of the apo-rFnBPA(189-505) from Staphylococcus aureus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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