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PDBsum entry 1fhc
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C-terminal domains of factor h
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PDB id
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1fhc
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Theoretical model |
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PDB id:
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C-terminal domains of factor h
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Title:
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C3d and heparin binding complement factor h domains scr19-20
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Structure:
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Complement factor h. Chain: a. Fragment: scr domains 19-20. Synonym: ccp19-20, scr19-20, sushi19-20
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Source:
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Homo sapiens. Human
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Authors:
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T.S.Jokiranta,J.Hellwage,M.A.Friese,T.U.Wolk,E.Kampen, P.F.Zipfel,S.Meri
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Key ref:
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J.Hellwage
et al.
(2002).
Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H.
J Immunol,
169,
6935-6944.
PubMed id:
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Date:
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10-Mar-99
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Release date:
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18-Mar-03
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PROCHECK
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Headers
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References
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P08603
(CFAH_HUMAN) -
Complement factor H
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Seq:
Struc:
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1231 a.a.
127 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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J Immunol
169:6935-6944
(2002)
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PubMed id:
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Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H.
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J.Hellwage,
T.S.Jokiranta,
M.A.Friese,
T.U.Wolk,
E.Kampen,
P.F.Zipfel,
S.Meri.
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ABSTRACT
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Factor H (FH) is a potent suppressor of the alternative pathway of C in plasma
and when bound to sialic acid- or glycosaminoglycan-rich surfaces. Of the three
interaction sites on FH for C3b, one interacts with the C3d part of C3b. In this
study, we generated recombinant constructs of FH and FH-related proteins (FHR)
to define the sites required for binding to C3d. In FH, the C3d-binding site was
localized by surface plasmon resonance analysis to the most C-terminal short
consensus repeat domain (SCR) 20. To identify amino acids of FH involved in
binding to C3d and heparin, we compared the sequences of FH and FHRs and
constructed a homology-based molecular model of SCR19-20 of FH. Subsequently, we
created an SCR15-20 mutant with substitutions in five amino acids that were
predicted to be involved in the binding interactions. These mutations reduced
binding of the SCR15-20 construct to both C3b/C3d and heparin. Binding of the
wild-type SCR15-20, but not the residual binding of the mutated SCR15-20, to C3d
was inhibited by heparin. This indicates that the heparin- and C3d-binding sites
are overlapping. Our results suggest that a region in the most C-terminal domain
of FH is involved in target recognition by binding to C3b and surface
polyanions. Mutations in this region, as recently reported in patients with
familial hemolytic uremic syndrome, may lead to indiscriminatory C attack
against self cells.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Siegel,
T.Hallström,
C.Skerka,
H.Eberhardt,
B.Uzonyi,
T.Beckhaus,
M.Karas,
R.Wallich,
B.Stevenson,
P.F.Zipfel,
and
P.Kraiczy
(2010).
Complement factor H-related proteins CFHR2 and CFHR5 represent novel ligands for the infection-associated CRASP proteins of Borrelia burgdorferi.
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PLoS One,
5,
e13519.
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Z.Zhang,
Y.Li,
S.Xu,
F.Chen,
L.Zhang,
B.Jiang,
and
X.Chen
(2010).
Fusion to chicken C3d enhances the immunogenicity of the M2 protein of avian influenza virus.
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Virol J,
7,
89.
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M.J.Lehtinen,
A.L.Rops,
D.E.Isenman,
J.van der Vlag,
and
T.S.Jokiranta
(2009).
Mutations of factor H impair regulation of surface-bound C3b by three mechanisms in atypical hemolytic uremic syndrome.
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J Biol Chem,
284,
15650-15658.
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M.K.Liszewski,
M.K.Leung,
R.Hauhart,
C.J.Fang,
P.Bertram,
and
J.P.Atkinson
(2009).
Smallpox inhibitor of complement enzymes (SPICE): dissecting functional sites and abrogating activity.
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J Immunol,
183,
3150-3159.
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M.Mihlan,
S.Stippa,
M.Józsi,
and
P.F.Zipfel
(2009).
Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H.
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Cell Death Differ,
16,
1630-1640.
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S.Buelli,
M.Abbate,
M.Morigi,
D.Moioli,
C.Zanchi,
M.Noris,
C.Zoja,
C.D.Pusey,
P.F.Zipfel,
and
G.Remuzzi
(2009).
Protein load impairs factor H binding promoting complement-dependent dysfunction of proximal tubular cells.
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Kidney Int,
75,
1050-1059.
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C.A.Brissette,
A.E.Cooley,
L.H.Burns,
S.P.Riley,
A.Verma,
M.E.Woodman,
T.Bykowski,
and
B.Stevenson
(2008).
Lyme borreliosis spirochete Erp proteins, their known host ligands, and potential roles in mammalian infection.
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Int J Med Microbiol,
298,
257-267.
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C.Siegel,
J.Schreiber,
K.Haupt,
C.Skerka,
V.Brade,
M.M.Simon,
B.Stevenson,
R.Wallich,
P.F.Zipfel,
and
P.Kraiczy
(2008).
Deciphering the ligand-binding sites in the Borrelia burgdorferi complement regulator-acquiring surface protein 2 required for interactions with the human immune regulators factor H and factor H-like protein 1.
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J Biol Chem,
283,
34855-34863.
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D.A.Falcão,
E.S.Reis,
D.Paixão-Cavalcante,
M.T.Amano,
M.I.Delcolli,
M.P.Florido,
J.A.Albuquerque,
D.Moraes-Vasconcelos,
A.J.Duarte,
A.S.Grumach,
and
L.Isaac
(2008).
Deficiency of the human complement regulatory protein factor h associated with low levels of component C9.
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Scand J Immunol,
68,
445-455.
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H.G.Hocking,
A.P.Herbert,
D.Kavanagh,
D.C.Soares,
V.P.Ferreira,
M.K.Pangburn,
D.Uhrín,
and
P.N.Barlow
(2008).
Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations.
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J Biol Chem,
283,
9475-9487.
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PDB codes:
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M.Józsi,
and
P.F.Zipfel
(2008).
Factor H family proteins and human diseases.
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Trends Immunol,
29,
380-387.
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M.Józsi,
M.Oppermann,
J.D.Lambris,
and
P.F.Zipfel
(2007).
The C-terminus of complement factor H is essential for host cell protection.
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Mol Immunol,
44,
2697-2706.
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R.E.Saunders,
C.Abarrategui-Garrido,
V.Frémeaux-Bacchi,
E.Goicoechea de Jorge,
T.H.Goodship,
M.López Trascasa,
M.Noris,
I.M.Ponce Castro,
G.Remuzzi,
S.Rodríguez de Córdoba,
P.Sánchez-Corral,
C.Skerka,
P.F.Zipfel,
and
S.J.Perkins
(2007).
The interactive Factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and Factor I mutations with structural models.
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Hum Mutat,
28,
222-234.
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T.Manabe,
and
Y.Jin
(2007).
Analysis of protein/polypeptide interactions in human plasma using nondenaturing micro-2-DE followed by 3-D SDS-PAGE and MS.
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Electrophoresis,
28,
2065-2079.
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F.Vaziri-Sani,
L.Holmberg,
A.G.Sjöholm,
A.C.Kristoffersson,
M.Manea,
V.Frémeaux-Bacchi,
I.Fehrman-Ekholm,
R.Raafat,
and
D.Karpman
(2006).
Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome.
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Kidney Int,
69,
981-988.
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J.Caprioli,
M.Noris,
S.Brioschi,
G.Pianetti,
F.Castelletti,
P.Bettinaglio,
C.Mele,
E.Bresin,
L.Cassis,
S.Gamba,
F.Porrati,
S.Bucchioni,
G.Monteferrante,
C.J.Fang,
M.K.Liszewski,
D.Kavanagh,
J.P.Atkinson,
and
G.Remuzzi
(2006).
Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.
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Blood,
108,
1267-1279.
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N.Besbas,
D.Karpman,
D.Landau,
C.Loirat,
W.Proesmans,
G.Remuzzi,
G.Rizzoni,
C.M.Taylor,
N.Van de Kar,
and
L.B.Zimmerhackl
(2006).
A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders.
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Kidney Int,
70,
423-431.
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R.E.Saunders,
T.H.Goodship,
P.F.Zipfel,
and
S.J.Perkins
(2006).
An interactive web database of factor H-associated hemolytic uremic syndrome mutations: insights into the structural consequences of disease-associated mutations.
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Hum Mutat,
27,
21-30.
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T.S.Jokiranta,
V.P.Jaakola,
M.J.Lehtinen,
M.Pärepalo,
S.Meri,
and
A.Goldman
(2006).
Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome.
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EMBO J,
25,
1784-1794.
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PDB code:
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F.Vaziri-Sani,
J.Hellwage,
P.F.Zipfel,
A.G.Sjöholm,
R.Iancu,
and
D.Karpman
(2005).
Factor H binds to washed human platelets.
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J Thromb Haemost,
3,
154-162.
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J.Caprioli,
L.Peng,
and
G.Remuzzi
(2005).
The hemolytic uremic syndromes.
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Curr Opin Crit Care,
11,
487-492.
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J.K.Mitsuyoshi,
Y.Hu,
and
S.T.Test
(2005).
Role of complement receptor type 2 and endogenous complement in the humoral immune response to conjugates of complement C3d and pneumococcal serotype 14 capsular polysaccharide.
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Infect Immun,
73,
7311-7316.
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T.S.Jokiranta,
Z.Z.Cheng,
H.Seeberger,
M.Jòzsi,
S.Heinen,
M.Noris,
G.Remuzzi,
R.Ormsby,
D.L.Gordon,
S.Meri,
J.Hellwage,
and
P.F.Zipfel
(2005).
Binding of complement factor H to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site.
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Am J Pathol,
167,
1173-1181.
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C.L.Davis
(2004).
Evaluation of the living kidney donor: current perspectives.
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Am J Kidney Dis,
43,
508-530.
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V.K.Ganesh,
S.A.Smith,
G.J.Kotwal,
and
K.H.Murthy
(2004).
Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.
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Proc Natl Acad Sci U S A,
101,
8924-8929.
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PDB code:
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H.P.Neumann,
M.Salzmann,
B.Bohnert-Iwan,
T.Mannuelian,
C.Skerka,
D.Lenk,
B.U.Bender,
M.Cybulla,
P.Riegler,
A.Königsrainer,
U.Neyer,
A.Bock,
U.Widmer,
D.A.Male,
G.Franke,
and
P.F.Zipfel
(2003).
Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries.
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J Med Genet,
40,
676-681.
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P.F.Zipfel,
H.P.Neumann,
and
M.Józsi
(2003).
Genetic screening in haemolytic uraemic syndrome.
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Curr Opin Nephrol Hypertens,
12,
653-657.
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R.L.Rich,
and
D.G.Myszka
(2003).
A survey of the year 2002 commercial optical biosensor literature.
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J Mol Recognit,
16,
351-382.
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V.Pandiripally,
L.Wei,
C.Skerka,
P.F.Zipfel,
and
D.Cue
(2003).
Recruitment of complement factor H-like protein 1 promotes intracellular invasion by group A streptococci.
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Infect Immun,
71,
7119-7128.
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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.
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Links
