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PDBsum entry 3d5o
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protein ligands Protein-protein interface(s) links
Immune system PDB id
3d5o

 

 

 

 

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Contents
Protein chains
204 a.a. *
171 a.a. *
Ligands
SO4 ×16
NAG ×5
GOL
Waters ×31
* Residue conservation analysis
PDB id:
3d5o
Name: Immune system
Title: Structural recognition and functional activation of fcrr by innate pentraxins
Structure: Serum amyloid p-component. Chain: a, b, c, d, e. Synonym: sap, 9.5s alpha-1-glycoprotein, serum amyloid p-component(1- 203). Engineered: yes. Low affinity immunoglobulin gamma fc region receptor ii-a. Chain: f. Synonym: igg fc receptor ii-a, fc-gamma rii-a, fc-gamma-riia, fcrii- a, cdw32.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: fcgr2a, cd32, fcg2, fcgr2a1, igfr2. Expression_system_taxid: 562
Resolution:
2.80Å     R-factor:   0.207     R-free:   0.279
Authors: J.Lu,L.L.Marnell,K.D.Marjon,C.Mold,T.W.Du Clos,P.D.Sun
Key ref:
J.Lu et al. (2008). Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature, 456, 989-992. PubMed id: 19011614 DOI: 10.1038/nature07468
Date:
16-May-08     Release date:   11-Nov-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P02743  (SAMP_HUMAN) -  Serum amyloid P-component from Homo sapiens
Seq:
Struc: 		223 a.a.
204 a.a.
Protein chain
Pfam   ArchSchema ?
P12318  (FCG2A_HUMAN) -  Low affinity immunoglobulin gamma Fc region receptor II-a from Homo sapiens
Seq:
Struc: 		317 a.a.
171 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1038/nature07468 Nature 456:989-992 (2008)
PubMed id: 19011614  
 
 
Structural recognition and functional activation of FcgammaR by innate pentraxins.
J.Lu, L.L.Marnell, K.D.Marjon, C.Mold, T.W.Du Clos, P.D.Sun.
 
  ABSTRACT  
 
Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q (refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell-surface Fcgamma receptors (FcgammaR) and activate leukocyte-mediated phagocytosis. Here we describe the structural mechanism for pentraxin's binding to FcgammaR and its functional activation of FcgammaR-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and FcgammaRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and FcgammaRIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for FcgammaR isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for FcgammaR binding and the inhibition of immune-complex-mediated phagocytosis by soluble pentraxins. These results establish antibody-like functions for pentraxins in the FcgammaR pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Crystal structure of SAP–Fc bold gamma-RIIa complex. a–c, The view is from the face (a) and sides (b, c) of SAP; in c only the receptor contact A and C subunits are highlighted. The five SAP subunits are shown in yellow with ridge helices in red, and Fc RIIa is coloured blue. The interface is represented by a molecular surface in green. The Ca^2+-binding and ligand-binding sites on SAP are highlighted in magenta. d, Comparison between the free (green) and receptor-bound (yellow) SAP, and between the free (wheat) and SAP-bound (blue) Fc RIIa structures. For clarity, only the A subunit is shown from the superposition of SAP pentamer. The BC loop (residues 28–35) of the D1 domain is indicated. 		Figure 3.
Figure 3: The binding interfaces between SAP and Fc bold gamma-RIIa. a, The interface between the D1 domain of Fc RIIa (blue and magenta) and the A subunit of SAP (yellow and green) is shown, with participating side residues shown as sticks. Hydrogen-bond interactions are represented by red dashed lines. b, The interface between the D2 domain of Fc RIIa and the C subunit of SAP.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nature (2008, 456, 989-992) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21388349 A.Inforzato, S.Jaillon, F.Moalli, E.Barbati, E.Bonavita, B.Bottazzi, A.Mantovani, and C.Garlanda (2011).
The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling.
  Tissue Antigens, 77, 271-282.  
21785456 A.Mantovani, M.A.Cassatella, C.Costantini, and S.Jaillon (2011).
Neutrophils in the activation and regulation of innate and adaptive immunity.
  Nat Rev Immunol, 11, 519-531.  
21468143 B.Rhodes, B.G.Fürnrohr, and T.J.Vyse (2011).
C-reactive protein in rheumatology: biology and genetics.
  Nat Rev Rheumatol, 7, 282-289.  
21383176 J.Lu, K.D.Marjon, L.L.Marnell, R.Wang, C.Mold, T.W.Du Clos, and P.Sun (2011).
Recognition and functional activation of the human IgA receptor (FcalphaRI) by C-reactive protein.
  Proc Natl Acad Sci U S A, 108, 4974-4979.  
21044893 L.A.Murray, Q.Chen, M.S.Kramer, D.P.Hesson, R.L.Argentieri, X.Peng, M.Gulati, R.J.Homer, T.Russell, N.van Rooijen, J.A.Elias, C.M.Hogaboam, and E.L.Herzog (2011).
TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P.
  Int J Biochem Cell Biol, 43, 154-162.  
20683616 L.Deban, S.Jaillon, C.Garlanda, B.Bottazzi, and A.Mantovani (2011).
Pentraxins in innate immunity: lessons from PTX3.
  Cell Tissue Res, 343, 237-249.  
  21223349 W.O.Pereira, and G.P.Amarante-Mendes (2011).
Apoptosis: a programme of cell death or cell disposal?
  Scand J Immunol, 73, 401-407.  
  21151582 X.Z.Hu, T.T.Wright, N.R.Jones, T.N.Ramos, G.A.Skibinski, M.A.McCrory, S.R.Barnum, and A.J.Szalai (2011).
Inhibition of Experimental Autoimmune Encephalomyelitis in Human C-Reactive Protein Transgenic Mice Is FcγRIIB Dependent.
  Autoimmune Dis, 2011, 484936.  
19968561 B.Bottazzi, A.Doni, C.Garlanda, and A.Mantovani (2010).
An integrated view of humoral innate immunity: pentraxins as a paradigm.
  Annu Rev Immunol, 28, 157-183.  
20973705 C.Kroupis, M.Theodorou, A.Chaidaroglou, M.Dalamaga, S.C.Oliveira, D.V.Cokkinos, D.Degiannis, and A.Manginas (2010).
The association between a common FCGR2A polymorphism and C-reactive protein and coronary artery disease revisited.
  Genet Test Mol Biomarkers, 14, 839-846.  
20829368 F.Moalli, A.Doni, L.Deban, T.Zelante, S.Zagarella, B.Bottazzi, L.Romani, A.Mantovani, and C.Garlanda (2010).
Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus.
  Blood, 116, 5170-5180.  
20146709 H.A.Niederer, M.R.Clatworthy, L.C.Willcocks, and K.G.Smith (2010).
FcgammaRIIB, FcgammaRIIIB, and systemic lupus erythematosus.
  Ann N Y Acad Sci, 1183, 69-88.  
20019744 I.K.Poon, M.D.Hulett, and C.R.Parish (2010).
Molecular mechanisms of late apoptotic/necrotic cell clearance.
  Cell Death Differ, 17, 381-397.  
20414206 K.G.Smith, and M.R.Clatworthy (2010).
FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications.
  Nat Rev Immunol, 10, 328-343.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
  20368175 A.P.Castaño, S.L.Lin, T.Surowy, B.T.Nowlin, S.A.Turlapati, T.Patel, A.Singh, S.Li, M.L.Lupher, and J.S.Duffield (2009).
Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo.
  Sci Transl Med, 1, 5ra13.  
19915573 K.Asano, T.Matsushita, J.Umeno, N.Hosono, A.Takahashi, T.Kawaguchi, T.Matsumoto, T.Matsui, Y.Kakuta, Y.Kinouchi, T.Shimosegawa, M.Hosokawa, Y.Arimura, Y.Shinomura, Y.Kiyohara, T.Tsunoda, N.Kamatani, M.Iida, Y.Nakamura, and M.Kubo (2009).
A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population.
  Nat Genet, 41, 1325-1329.  
19691552 R.J.Pleass (2009).
Fc-receptors and immunity to malaria: from models to vaccines.
  Parasite Immunol, 31, 529-538.  
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.

 

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