PDBsum entry 1n67

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protein metals links
Cell adhesion PDB id
Protein chain
332 a.a. *
_MG ×3
Waters ×376
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: Clumping factor a from staphylococcus aureus
Structure: Clumping factor. Chain: a. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562
1.90Å     R-factor:   0.206     R-free:   0.256
Authors: C.C.S.Deivanayagam,E.R.Wann,W.Chen,M.Carson,K.R.Rajashankar, M.Hook,S.V.L.Narayana
Key ref:
C.C.Deivanayagam et al. (2002). A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A. EMBO J, 21, 6660-6672. PubMed id: 12485987 DOI: 10.1093/emboj/cdf619
08-Nov-02     Release date:   04-Mar-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q53653  (CLFA_STAAE) -  Clumping factor A
933 a.a.
332 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell wall   1 term 
  Biological process     cell adhesion   1 term 


DOI no: 10.1093/emboj/cdf619 EMBO J 21:6660-6672 (2002)
PubMed id: 12485987  
A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A.
C.C.Deivanayagam, E.R.Wann, W.Chen, M.Carson, K.R.Rajashankar, M.Höök, S.V.Narayana.
We report here the crystal structure of the minimal ligand-binding segment of the Staphylococcus aureus MSCRAMM, clumping factor A. This fibrinogen-binding segment contains two similarly folded domains. The fold observed is a new variant of the immunoglobulin motif that we have called DE-variant or the DEv-IgG fold. This subgroup includes the ligand-binding domain of the collagen-binding S.aureus MSCRAMM CNA, and many other structures previously classified as jelly rolls. Structure predictions suggest that the four fibrinogen-binding S.aureus MSCRAMMs identified so far would also contain the same DEv-IgG fold. A systematic docking search using the C-terminal region of the fibrinogen gamma-chain as a probe suggested that a hydrophobic pocket formed between the two DEv-IgG domains of the clumping factor as the ligand-binding site. Mutagenic substitution of residues Tyr256, Pro336, Tyr338 and Lys389 in the clumping factor, which are proposed to contact the terminal residues (408)AGDV(411) of the gamma-chain, resulted in proteins with no or markedly reduced affinity for fibrinogen.
  Selected figure(s)  
Figure 2.
Figure 2 Domain structure of rClfA[(221–559)]. (A) Stereo ribbon diagram of the ClfA crystal structure. In the two independent domains, the -strands A–G are colored in rainbow fashion. The N- and C-termini and the boundary between the domains indicated by Y369 are also labeled. Each domain has a coordinate axis defined by the relative orientation of the sheets. The long, black axis is the average sheet direction. The silver spheres represent the metal ions. (B) Structure-based sequence alignment of the ClfA N2 and N3 domains. The strands A–G are marked with arrows colored as in the ribbon diagrams. Ranges of residues where all C superpose within 1.5 Å are boxed. Hydrophobic residues are black, polar are blue and charged are red. Identical residues are highlighted with gray. (C) Superposition of the ClfA N2 and N3 domains. Stereo ribbon diagrams of the two domains are overlaid. -strands A–G are labeled and colored as above. The coil regions of the first domain are dark gray, the coil linking the two domains is light gray and the coils of the second domain are shown in white. The average sheet direction is aligned with the y-axis, and the average direction between adjacent strands with the x-axis.
Figure 4.
Figure 4 Topology of the IgG and MSCRAMM domains. Ribbon diagrams of the labeled strands A–G colored in rainbow fashion as in Figure 2. The corresponding topology diagram of the structure is shown to the right. (A) IgG-C domain. (B) ClfA N2 domain [rClfA[(221–559)]]. (C) CNA19 domain (CNA[169–318]). (D) Superposition of IgG, rClfA[(221–559)]-N2 and CNA[169–318].
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 6660-6672) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280131 E.Matsuoka, Y.Tanaka, M.Kuroda, Y.Shouji, T.Ohta, I.Tanaka, and M.Yao (2011).
Crystal structure of the functional region of Uro-adherence factor A from Staphylococcus saprophyticus reveals participation of the B domain in ligand binding.
  Protein Sci, 20, 406-416.
PDB codes: 3irp 3irz 3is1
21347378 H.A.Choy, M.M.Kelley, J.Croda, J.Matsunaga, J.T.Babbitt, A.I.Ko, M.Picardeau, and D.A.Haake (2011).
The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans.
  PLoS One, 6, e16879.  
21055949 H.J.Kang, and E.N.Baker (2011).
Intramolecular isopeptide bonds: protein crosslinks built for stress?
  Trends Biochem Sci, 36, 229-237.  
21404359 K.Vengadesan, and S.V.Narayana (2011).
Structural biology of gram-positive bacterial adhesins.
  Protein Sci, 20, 759-772.  
  20887232 M.I.Krevvata, A.Spiliopoulou, E.D.Anastassiou, N.Karamanos, and F.Kolonitsiou (2011).
Adherence of Staphylococcus epidermidis to human endothelial cells is associated with a polysaccharidic component of its extracellular mucous layer.
  Connect Tissue Res, 52, 183-189.  
21219469 Y.P.Lin, S.P.McDonough, Y.Sharma, and Y.F.Chang (2011).
Leptospira immunoglobulin-like protein B (LigB) binding to the C-terminal fibrinogen αC domain inhibits fibrin clot formation, platelet adhesion and aggregation.
  Mol Microbiol, 79, 1063-1076.  
20090838 E.M.Barbu, V.K.Ganesh, S.Gurusiddappa, R.C.Mackenzie, T.J.Foster, T.C.Sudhof, and M.Höök (2010).
beta-Neurexin is a ligand for the Staphylococcus aureus MSCRAMM SdrC.
  PLoS Pathog, 6, e1000726.  
20515471 F.M.Burke, N.McCormack, S.Rindi, P.Speziale, and T.J.Foster (2010).
Fibronectin-binding protein B variation in Staphylococcus aureus.
  BMC Microbiol, 10, 160.  
20007717 J.A.Geoghegan, V.K.Ganesh, E.Smeds, X.Liang, M.Höök, and T.J.Foster (2010).
Molecular characterization of the interaction of staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMM) ClfA and Fbl with fibrinogen.
  J Biol Chem, 285, 6208-6216.  
20497507 L.J.Brady, S.E.Maddocks, M.R.Larson, N.Forsgren, K.Persson, C.C.Deivanayagam, and H.F.Jenkinson (2010).
The changing faces of Streptococcus antigen I/II polypeptide family adhesins.
  Mol Microbiol, 77, 276-286.  
20817646 M.Haim, A.Trost, C.J.Maier, G.Achatz, S.Feichtner, H.Hintner, J.W.Bauer, and K.Onder (2010).
Cytokeratin 8 interacts with clumping factor B: a new possible virulence factor target.
  Microbiology, 156, 3710-3721.  
20100856 P.S.Hair, C.G.Echague, A.M.Sholl, J.A.Watkins, J.A.Geoghegan, T.J.Foster, and K.M.Cunnion (2010).
Clumping factor A interaction with complement factor I increases C3b cleavage on the bacterial surface of Staphylococcus aureus and decreases complement-mediated phagocytosis.
  Infect Immun, 78, 1717-1727.  
20584910 S.Ramboarina, J.A.Garnett, M.Zhou, Y.Li, Z.Peng, J.D.Taylor, W.C.Lee, A.Bodey, J.W.Murray, Y.Alguel, J.Bergeron, B.Bardiaux, E.Sawyer, R.Isaacson, C.Tagliaferri, E.Cota, M.Nilges, P.Simpson, T.Ruiz, H.Wu, and S.Matthews (2010).
Structural insights into serine-rich fimbriae from Gram-positive bacteria.
  J Biol Chem, 285, 32446-32457.
PDB codes: 2kub 2x12
19737906 A.P.Hendrickx, M.van Luit-Asbroek, C.M.Schapendonk, W.J.van Wamel, J.C.Braat, L.M.Wijnands, M.J.Bonten, and R.J.Willems (2009).
SgrA, a nidogen-binding LPXTG surface adhesin implicated in biofilm formation, and EcbA, a collagen binding MSCRAMM, are two novel adhesins of hospital-acquired Enterococcus faecium.
  Infect Immun, 77, 5097-5106.  
19805181 H.J.Kang, N.G.Paterson, A.H.Gaspar, H.Ton-That, and E.N.Baker (2009).
The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds.
  Proc Natl Acad Sci U S A, 106, 16967-16971.
PDB codes: 3hr6 3htl
19389755 J.Sillanpää, S.R.Nallapareddy, J.Houston, V.K.Ganesh, A.Bourgogne, K.V.Singh, B.E.Murray, and M.Höök (2009).
A family of fibrinogen-binding MSCRAMMs from Enterococcus faecalis.
  Microbiology, 155, 2390-2400.  
  19527885 K.A.Kline, S.Fälker, S.Dahlberg, S.Normark, and B.Henriques-Normark (2009).
Bacterial adhesins in host-microbe interactions.
  Cell Host Microbe, 5, 580-592.  
19995192 P.Speziale, G.Pietrocola, S.Rindi, M.Provenzano, G.Provenza, A.Di Poto, L.Visai, and C.R.Arciola (2009).
Structural and functional role of Staphylococcus aureus surface components recognizing adhesive matrix molecules of the host.
  Future Microbiol, 4, 1337-1352.  
18466610 A.Loughman, T.Sweeney, F.M.Keane, G.Pietrocola, P.Speziale, and T.J.Foster (2008).
Sequence diversity in the A domain of Staphylococcus aureus fibronectin-binding protein A.
  BMC Microbiol, 8, 74.  
18493318 E.Josefsson, J.Higgins, T.J.Foster, and A.Tarkowski (2008).
Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence.
  PLoS ONE, 3, e2206.  
18375547 E.O'Neill, C.Pozzi, P.Houston, H.Humphreys, D.A.Robinson, A.Loughman, T.J.Foster, and J.P.O'Gara (2008).
A novel Staphylococcus aureus biofilm phenotype mediated by the fibronectin-binding proteins, FnBPA and FnBPB.
  J Bacteriol, 190, 3835-3850.  
18832325 J.Sillanpää, S.R.Nallapareddy, V.P.Prakash, X.Qin, M.Höök, G.M.Weinstock, and B.E.Murray (2008).
Identification and phenotypic characterization of a second collagen adhesin, Scm, and genome-based identification and analysis of 13 other predicted MSCRAMMs, including four distinct pilus loci, in Enterococcus faecium.
  Microbiology, 154, 3199-3211.  
18602404 K.Tan, M.Duquette, J.H.Liu, J.Lawler, and J.H.Wang (2008).
The crystal structure of the heparin-binding reelin-N domain of f-spondin.
  J Mol Biol, 381, 1213-1223.
PDB code: 3coo
17991749 M.G.Bowden, A.P.Heuck, K.Ponnuraj, E.Kolosova, D.Choe, S.Gurusiddappa, S.V.Narayana, A.E.Johnson, and M.Höök (2008).
Evidence for the "dock, lock, and latch" ligand binding mechanism of the staphylococcal microbial surface component recognizing adhesive matrix molecules (MSCRAMM) SdrG.
  J Biol Chem, 283, 638-647.
PDB code: 2ral
19043557 V.K.Ganesh, J.J.Rivera, E.Smeds, Y.P.Ko, M.G.Bowden, E.R.Wann, S.Gurusiddappa, J.R.Fitzgerald, and M.Höök (2008).
A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics.
  PLoS Pathog, 4, e1000226.
PDB code: 2vr3
17302800 F.M.Keane, A.Loughman, V.Valtulina, M.Brennan, P.Speziale, and T.J.Foster (2007).
Fibrinogen and elastin bind to the same region within the A domain of fibronectin binding protein A, an MSCRAMM of Staphylococcus aureus.
  Mol Microbiol, 63, 711-723.  
17296754 H.A.Choy, M.M.Kelley, T.L.Chen, A.K.Møller, J.Matsunaga, and D.A.Haake (2007).
Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen.
  Infect Immun, 75, 2441-2450.  
17557326 K.Ponnuraj, and S.V.Narayana (2007).
Crystal structure of ACE19, the collagen binding subdomain of Enterococus faecalis surface protein ACE.
  Proteins, 69, 199-203.
PDB code: 2okm
17392280 Q.Liu, K.Ponnuraj, Y.Xu, V.K.Ganesh, J.Sillanpää, B.E.Murray, S.V.Narayana, and M.Höök (2007).
The Enterococcus faecalis MSCRAMM ACE binds its ligand by the Collagen Hug model.
  J Biol Chem, 282, 19629-19637.
PDB code: 2z1p
17438036 S.R.Nallapareddy, J.Sillanpää, V.K.Ganesh, M.Höök, and B.E.Murray (2007).
Inhibition of Enterococcus faecium adherence to collagen by antibodies against high-affinity binding subdomains of Acm.
  Infect Immun, 75, 3192-3196.  
17697995 V.Krishnan, A.H.Gaspar, N.Ye, A.Mandlik, H.Ton-That, and S.V.Narayana (2007).
An IgG-like domain in the minor pilin GBS52 of Streptococcus agalactiae mediates lung epithelial cell adhesion.
  Structure, 15, 893-903.
PDB codes: 2pz4 3phs
16524923 L.A.Marraffini, A.C.Dedent, and O.Schneewind (2006).
Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria.
  Microbiol Mol Biol Rev, 70, 192-221.  
17016560 S.R.Nallapareddy, K.V.Singh, J.Sillanpää, D.A.Garsin, M.Höök, S.L.Erlandsen, and B.E.Murray (2006).
Endocarditis and biofilm-associated pili of Enterococcus faecalis.
  J Clin Invest, 116, 2799-2807.  
16045623 A.Loughman, J.R.Fitzgerald, M.P.Brennan, J.Higgins, R.Downer, D.Cox, and T.J.Foster (2005).
Roles for fibrinogen, immunoglobulin and complement in platelet activation promoted by Staphylococcus aureus clumping factor A.
  Mol Microbiol, 57, 804-818.  
16077117 S.R.Nallapareddy, H.Wenxiang, G.M.Weinstock, and B.E.Murray (2005).
Molecular characterization of a widespread, pathogenic, and antibiotic resistance-receptive Enterococcus faecalis lineage and dissemination of its putative pathogenicity island.
  J Bacteriol, 187, 5709-5718.  
16362049 Y.Zong, Y.Xu, X.Liang, D.R.Keene, A.Höök, S.Gurusiddappa, M.Höök, and S.V.Narayana (2005).
A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen.
  EMBO J, 24, 4224-4236.
PDB codes: 2f68 2f6a
15385531 E.J.Walsh, L.M.O'Brien, X.Liang, M.Hook, and T.J.Foster (2004).
Clumping factor B, a fibrinogen-binding MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesin of Staphylococcus aureus, also binds to the tail region of type I cytokeratin 10.
  J Biol Chem, 279, 50691-50699.  
15234962 F.M.Roche, R.Downer, F.Keane, P.Speziale, P.W.Park, and T.J.Foster (2004).
The N-terminal A domain of fibronectin-binding proteins A and B promotes adhesion of Staphylococcus aureus to elastin.
  J Biol Chem, 279, 38433-38440.  
15093830 H.Remaut, and G.Waksman (2004).
Structural biology of bacterial pathogenesis.
  Curr Opin Struct Biol, 14, 161-170.  
15556714 M.Nilsson, J.Bjerketorp, B.Guss, and L.Frykberg (2004).
A fibrinogen-binding protein of Staphylococcus lugdunensis.
  FEMS Microbiol Lett, 241, 87-93.  
15456768 Y.Xu, X.Liang, Y.Chen, T.M.Koehler, and M.Höök (2004).
Identification and biochemical characterization of two novel collagen binding MSCRAMMs of Bacillus anthracis.
  J Biol Chem, 279, 51760-51768.  
14567919 K.Ponnuraj, M.G.Bowden, S.Davis, S.Gurusiddappa, D.Moore, D.Choe, Y.Xu, M.Hook, and S.V.Narayana (2003).
A "dock, lock, and latch" structural model for a staphylococcal adhesin binding to fibrinogen.
  Cell, 115, 217-228.
PDB codes: 1r17 1r19
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.