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protein metals Protein-protein interface(s) links
Immune system PDB id
1pk6
Jmol
Contents
Protein chains
133 a.a. *
132 a.a. *
129 a.a. *
Metals
_CA
Waters ×198
* Residue conservation analysis
PDB id:
1pk6
Name: Immune system
Title: Globular head of the complement system protein c1q
Structure: Complement c1q subcomponent, a chain precursor. Chain: a. Synonym: c1q. Complement c1q subcomponent, b chain precursor. Chain: b. Synonym: c1q. Complement c1q subcomponent, c chain precursor. Chain: c. Synonym: c1q
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: serum. Other_details: serum
Biol. unit: Hexamer (from PQS)
Resolution:
1.85Å     R-factor:   0.201     R-free:   0.239
Authors: C.Gaboriaud,J.Juanhuix,A.Gruez,M.Lacroix,C.Darnault, D.Pignol,D.Verger,J.C.Fontecilla-Camps,G.J.Arlaud
Key ref:
C.Gaboriaud et al. (2003). The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem, 278, 46974-46982. PubMed id: 12960167 DOI: 10.1074/jbc.M307764200
Date:
05-Jun-03     Release date:   21-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P02745  (C1QA_HUMAN) -  Complement C1q subcomponent subunit A
Seq:
Struc: 		245 a.a.
133 a.a.
Protein chain
Pfam   ArchSchema ?
P02746  (C1QB_HUMAN) -  Complement C1q subcomponent subunit B
Seq:
Struc: 		253 a.a.
132 a.a.
Protein chain
Pfam   ArchSchema ?
P02747  (C1QC_HUMAN) -  Complement C1q subcomponent subunit C
Seq:
Struc: 		245 a.a.
129 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M307764200 J Biol Chem 278:46974-46982 (2003)
PubMed id: 12960167  
 
 
The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties.
C.Gaboriaud, J.Juanhuix, A.Gruez, M.Lacroix, C.Darnault, D.Pignol, D.Verger, J.C.Fontecilla-Camps, G.J.Arlaud.
 
  ABSTRACT  
 
C1q is a versatile recognition protein that binds to an amazing variety of immune and non-immune ligands and triggers activation of the classical pathway of complement. The crystal structure of the C1q globular domain responsible for its recognition properties has now been solved and refined to 1.9 A of resolution. The structure reveals a compact, almost spherical heterotrimeric assembly held together mainly by non-polar interactions, with a Ca2+ ion bound at the top. The heterotrimeric assembly of the C1q globular domain appears to be a key factor of the versatile recognition properties of this protein. Plausible three-dimensional models of the C1q globular domain in complex with two of its physiological ligands, C-reactive protein and IgG, are proposed, highlighting two of the possible recognition modes of C1q. The C1q/human IgG1 model suggests a critical role for the hinge region of IgG and for the relative orientation of its Fab domain in C1q binding.
 
  Selected figure(s)  
 
Figure 3.
FIG. 3. Surface properties of the C1q globular domain. A, side view of the heterotrimer seen from module A. B, side view seen from module B. C, side view seen from module C. The overall orientation of the trimer is similar to that in Fig. 1B. D, view of the heterotrimer seen from the top. The side chains of Arg, Lys, His, Asp, and Glu residues are shown in deep blue, light blue, green, red, and magenta, respectively. Hydrophobic residues (Ile, Leu, Val, Pro, Met) are shown in yellow, and aromatic residues (Phe, Trp, Tyr) are in orange. The lines in D indicate the approximate module boundaries. This figure was made using GRASP (59). 		Figure 5.
FIG. 5. The C1q-IgG1 interaction. A, space-filling representation of the proposed interacting faces of human IgG1 b12 (36, 37) and C1q head, showing their shape complementarity. The IgG Fc domain and Fab arms are indicated. Color coding for the mutated residues of IgG1 (9, 41, 42) is as follows. Major charged residues crucial for the interaction (Asp-270, Lys-322) are red, charged residues impairing the interaction (Lys-326, Glu-333) are blue, other crucial residues in the contacting zone (Pro-329, Pro-331) are magenta, and those in the hinge region (Leu-234, Leu-235) are black. The arginine residues of C1q B proposed as possible interaction site are displayed in light blue. B, same representation of the C1q/IgG1 assembly. C, overall view of the interaction between C1q and IgG1. The C1q model was constructed as described under "Experimental Procedures." The black arrow indicates the antigenic site. N124 indicates the position of the carbohydrate chain attached to the C1q A subunit. D, structure of Mcg (57) highlighting the inability of this IgG1 molecule to bind C1q. The residue color coding is the same as in A. The Fab arms are shown in green.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 46974-46982) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21352829 H.Païdassi, P.Tacnet-Delorme, M.Verneret, C.Gaboriaud, G.Houen, K.Duus, W.L.Ling, G.J.Arlaud, and P.Frachet (2011).
Investigations on the C1q-calreticulin-phosphatidylserine interactions yield new insights into apoptotic cell recognition.
  J Mol Biol, 408, 277-290.  
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.  
19807696 C.L.Basiglio, S.M.Arriaga, F.Pelusa, A.M.Almará, J.Kapitulnik, and A.D.Mottino (2010).
Complement activation and disease: protective effects of hyperbilirubinaemia.
  Clin Sci (Lond), 118, 99.  
19996152 C.Shimono, R.Manabe, T.Yamada, S.Fukuda, J.Kawai, Y.Furutani, K.Tsutsui, K.Ikenaka, Y.Hayashizaki, and K.Sekiguchi (2010).
Identification and characterization of nCLP2, a novel C1q family protein expressed in the central nervous system.
  J Biochem, 147, 565-579.  
20820193 H.Yang, J.Wang, J.Du, C.Zhong, D.Zhang, H.Guo, Y.Guo, and J.Ding (2010).
Structural basis of immunosuppression by the therapeutic antibody daclizumab.
  Cell Res, 20, 1361-1371.
PDB codes: 3nfp 3nfs
20152153 O.Sulák, G.Cioci, M.Delia, M.Lahmann, A.Varrot, A.Imberty, and M.Wimmerová (2010).
A TNF-like trimeric lectin domain from Burkholderia cenocepacia with specificity for fucosylated human histo-blood group antigens.
  Structure, 18, 59-72.
PDB code: 2wq4
19783065 R.Wallis, D.A.Mitchell, R.Schmid, W.J.Schwaeble, and A.H.Keeble (2010).
Paths reunited: Initiation of the classical and lectin pathways of complement activation.
  Immunobiology, 215, 1.  
20722630 Y.Abe, J.Gor, D.G.Bracewell, S.J.Perkins, and P.A.Dalby (2010).
Masking of the Fc region in human IgG4 by constrained X-ray scattering modelling: implications for antibody function and therapy.
  Biochem J, 432, 101-111.  
19494295 A.E.Phillips, J.Toth, A.W.Dodds, U.V.Girija, C.M.Furze, E.Pala, R.B.Sim, K.B.Reid, W.J.Schwaeble, R.Schmid, A.H.Keeble, and R.Wallis (2009).
Analogous interactions in initiating complexes of the classical and lectin pathways of complement.
  J Immunol, 182, 7708-7717.  
19144569 A.P.Sjöberg, L.A.Trouw, and A.M.Blom (2009).
Complement activation and inhibition: a delicate balance.
  Trends Immunol, 30, 83-90.  
19409097 A.Saladin, S.Fiorucci, P.Poulain, C.Prevost, and M.Zacharias (2009).
PTools: an opensource molecular docking library.
  BMC Struct Biol, 9, 27.  
19205000 B.Westereng, G.J.Coenen, T.E.Michaelsen, A.G.Voragen, A.B.Samuelsen, H.A.Schols, and S.H.Knutsen (2009).
Release and characterization of single side chains of white cabbage pectin and their complement-fixing activity.
  Mol Nutr Food Res, 53, 780-789.  
19023665 G.Verdone, A.Corazza, S.A.Colebrooke, D.Cicero, T.Eliseo, J.Boyd, R.Doliana, F.Fogolari, P.Viglino, A.Colombatti, I.D.Campbell, and G.Esposito (2009).
NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1.
  J Biomol NMR, 43, 79-96.
PDB code: 2ka3
19048248 J.E.Butler, N.Wertz, N.Deschacht, and I.Kacskovics (2009).
Porcine IgG: structure, genetics, and evolution.
  Immunogenetics, 61, 209-230.  
19075776 A.Agrawal, M.V.Suresh, S.K.Singh, and D.A.Ferguson (2008).
The protective function of human C-reactive protein in mouse models of Streptococcus pneumoniae infection.
  Endocr Metab Immune Disord Drug Targets, 8, 231-237.  
18510435 A.Banga, A.M.Bodles, N.Rasouli, G.Ranganathan, P.A.Kern, and R.J.Owens (2008).
Calcium is involved in formation of high molecular weight adiponectin.
  Metab Syndr Relat Disord, 6, 103-111.  
18318657 F.Alber, F.Förster, D.Korkin, M.Topf, and A.Sali (2008).
Integrating diverse data for structure determination of macromolecular assemblies.
  Annu Rev Biochem, 77, 443-477.  
  18250442 H.Païdassi, P.Tacnet-Delorme, V.Garlatti, C.Darnault, B.Ghebrehiwet, C.Gaboriaud, G.J.Arlaud, and P.Frachet (2008).
C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition.
  J Immunol, 180, 2329-2338.
PDB codes: 2jg8 2jg9
18313756 H.Y.Hwang, M.R.Duvall, S.Tomlinson, and R.J.Boackle (2008).
Highly specific inhibition of C1q globular-head binding to human IgG: a novel approach to control and regulate the classical complement pathway using an engineered single chain antibody variable fragment.
  Mol Immunol, 45, 2570-2580.  
18300248 M.A.Sheikh, J.A.Potter, K.A.Johnson, R.B.Sim, E.F.Boyd, and G.L.Taylor (2008).
Crystal structure of VC1805, a conserved hypothetical protein from a Vibrio cholerae pathogenicity island, reveals homology to human p32.
  Proteins, 71, 1563-1571.
PDB code: 2v1l
18400300 M.Li, R.R.Ager, D.A.Fraser, N.O.Tjokro, and A.J.Tenner (2008).
Development of a humanized C1q A chain knock-in mouse: assessment of antibody independent beta-amyloid induced complement activation.
  Mol Immunol, 45, 3244-3252.  
  18179779 P.Tacnet, E.C.Cheong, P.Goeltz, B.Ghebrehiwet, G.J.Arlaud, X.Y.Liu, and C.Lesieur (2008).
Trimeric reassembly of the globular domain of human C1q.
  Biochim Biophys Acta, 1784, 518-529.  
17991046 C.Dumestre-Pérard, J.Osmundson, C.Lemaire-Vieille, N.Thielens, A.Grives, B.Favier, F.Csopaki, M.Jamin, J.Gagnon, and J.Y.Cesbron (2007).
Activation of classical pathway of complement cascade by soluble oligomers of prion.
  Cell Microbiol, 9, 2870-2879.  
17929239 L.Roumenina, S.Bureeva, A.Kantardjiev, D.Karlinsky, J.E.Andia-Pravdivy, R.Sim, A.Kaplun, M.Popov, U.Kishore, and B.Atanasov (2007).
Complement C1q-target proteins recognition is inhibited by electric moment effectors.
  J Mol Recognit, 20, 405-415.  
17215869 V.Garlatti, N.Belloy, L.Martin, M.Lacroix, M.Matsushita, Y.Endo, T.Fujita, J.C.Fontecilla-Camps, G.J.Arlaud, N.M.Thielens, and C.Gaboriaud (2007).
Structural insights into the innate immune recognition specificities of L- and H-ficolins.
  EMBO J, 26, 623-633.
PDB codes: 2j0g 2j0h 2j0y 2j1g 2j2p 2j3f 2j3g 2j3o 2j3u 2j5z 2j60 2j61 2j64
16905106 D.M.Compaan, and S.G.Hymowitz (2006).
The crystal structure of the costimulatory OX40-OX40L complex.
  Structure, 14, 1321-1330.
PDB codes: 2hev 2hew 2hey
16619242 N.Danilova (2006).
The evolution of immune mechanisms.
  J Exp Zoolog B Mol Dev Evol, 306, 496-520.  
16323243 T.E.Michaelsen, J.E.Thommesen, O.Ihle, T.F.Gregers, R.H.Sandin, O.H.Brekke, and I.Sandlie (2006).
A mutant human IgG molecule with only one C1q binding site can activate complement and induce lysis of target cells.
  Eur J Immunol, 36, 129-138.  
16155912 T.Maeda, A.Jikko, M.Abe, T.Yokohama-Tamaki, H.Akiyama, S.Furukawa, M.Takigawa, and S.Wakisaka (2006).
Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes.
  J Cell Physiol, 206, 537-544.  
15654870 A.D.van Dijk, R.Boelens, and A.M.Bonvin (2005).
Data-driven docking for the study of biomolecular complexes.
  FEBS J, 272, 293-312.  
16135095 D.Bao, Z.Pang, and J.I.Morgan (2005).
The structure and proteolytic processing of Cbln1 complexes.
  J Neurochem, 95, 618-629.  
15982298 R.D.Sontheimer, E.Racila, and D.M.Racila (2005).
C1q: its functions within the innate and adaptive immune responses and its role in lupus autoimmunity.
  J Invest Dermatol, 125, 14-23.  
15140059 A.Steinø, C.S.Jørgensen, I.Laursen, and G.Houen (2004).
Interaction of C1q with the receptor calreticulin requires a conformational change in C1q.
  Scand J Immunol, 59, 485-495.  
15207504 C.Gaboriaud, N.M.Thielens, L.A.Gregory, V.Rossi, J.C.Fontecilla-Camps, and G.J.Arlaud (2004).
Structure and activation of the C1 complex of complement: unraveling the puzzle.
  Trends Immunol, 25, 368-373.  
15364058 U.Kishore, C.Gaboriaud, P.Waters, A.K.Shrive, T.J.Greenhough, K.B.Reid, R.B.Sim, and G.J.Arlaud (2004).
C1q and tumor necrosis factor superfamily: modularity and versatility.
  Trends Immunol, 25, 551-561.  
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.