 |
PDBsum entry 2hg0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Viral protein
|
PDB id
|
|
|
|
2hg0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
J Virol
80:11467-11474
(2006)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Crystal structure of the West Nile virus envelope glycoprotein.
|
|
G.E.Nybakken,
C.A.Nelson,
B.R.Chen,
M.S.Diamond,
D.H.Fremont.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The envelope glycoprotein (E) of West Nile virus (WNV) undergoes a
conformational rearrangement triggered by low pH that results in a class II
fusion event required for viral entry. Herein we present the 3.0-A crystal
structure of the ectodomain of WNV E, which reveals insights into the flavivirus
life cycle. We found that WNV E adopts a three-domain architecture that is
shared by the E proteins from dengue and tick-borne encephalitis viruses and
forms a rod-shaped configuration similar to that observed in immature flavivirus
particles. Interestingly, the single N-linked glycosylation site on WNV E is
displaced by a novel alpha-helix, which could potentially alter lectin-mediated
attachment. The localization of histidines within the hinge regions of E
implicates these residues in pH-induced conformational transitions. Most
strikingly, the WNV E ectodomain crystallized as a monomer, in contrast to other
flavivirus E proteins, which have crystallized as antiparallel dimers. WNV E
assembles in a crystalline lattice of perpendicular molecules, with the fusion
loop of one E protein buried in a hydrophobic pocket at the DI-DIII interface of
another. Dimeric E proteins pack their fusion loops into analogous pockets at
the dimer interface. We speculate that E proteins could pivot around the fusion
loop-pocket junction, allowing virion conformational transitions while
minimizing fusion loop exposure.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
D.W.Beasley
(2011).
Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus.
|
| |
Immunotherapy,
3,
269-285.
|
|
|
|
|
|
|
M.A.Martín-Acebes,
and
J.C.Saiz
(2011).
A West Nile virus mutant with increased resistance to acid-induced inactivation.
|
| |
J Gen Virol,
92,
831-840.
|
|
|
|
|
|
|
M.Laassri,
B.Bidzhieva,
J.Speicher,
A.G.Pletnev,
and
K.Chumakov
(2011).
Microarray hybridization for assessment of the genetic stability of chimeric West Nile/dengue 4 virus.
|
| |
J Med Virol,
83,
910-920.
|
|
|
|
|
|
|
A.J.Schuh,
L.Li,
R.B.Tesh,
B.L.Innis,
and
A.D.Barrett
(2010).
Genetic characterization of early isolates of Japanese encephalitis virus: genotype II has been circulating since at least 1951.
|
| |
J Gen Virol,
91,
95.
|
|
|
|
|
|
|
A.Zheng,
M.Umashankar,
and
M.Kielian
(2010).
In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions.
|
| |
PLoS Pathog,
6,
e1001157.
|
|
|
|
|
|
|
B.Kaufmann,
M.R.Vogt,
J.Goudsmit,
H.A.Holdaway,
A.A.Aksyuk,
P.R.Chipman,
R.J.Kuhn,
M.S.Diamond,
and
M.G.Rossmann
(2010).
Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354.
|
| |
Proc Natl Acad Sci U S A,
107,
18950-18955.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
I.A.Rodenhuis-Zybert,
J.Wilschut,
and
J.M.Smit
(2010).
Dengue virus life cycle: viral and host factors modulating infectivity.
|
| |
Cell Mol Life Sci,
67,
2773-2786.
|
|
|
|
|
|
|
J.M.Costin,
E.Jenwitheesuk,
S.M.Lok,
E.Hunsperger,
K.A.Conrads,
K.A.Fontaine,
C.R.Rees,
M.G.Rossmann,
S.Isern,
R.Samudrala,
and
S.F.Michael
(2010).
Structural optimization and de novo design of dengue virus entry inhibitory peptides.
|
| |
PLoS Negl Trop Dis,
4,
e721.
|
|
|
|
|
|
|
M.D.Dunn,
S.L.Rossi,
D.M.Carter,
M.R.Vogt,
E.Mehlhop,
M.S.Diamond,
and
T.M.Ross
(2010).
Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice.
|
| |
Virol J,
7,
95.
|
|
|
|
|
|
|
M.Kielian,
C.Chanel-Vos,
and
M.Liao
(2010).
Alphavirus Entry and Membrane Fusion.
|
| |
Viruses,
2,
796-825.
|
|
|
|
|
|
|
R.Hasebe,
T.Suzuki,
Y.Makino,
M.Igarashi,
S.Yamanouchi,
A.Maeda,
M.Horiuchi,
H.Sawa,
and
T.Kimura
(2010).
Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein.
|
| |
BMC Microbiol,
10,
165.
|
|
|
|
|
|
|
W.M.Wahala,
E.F.Donaldson,
R.de Alwis,
M.A.Accavitti-Loper,
R.S.Baric,
and
A.M.de Silva
(2010).
Natural strain variation and antibody neutralization of dengue serotype 3 viruses.
|
| |
PLoS Pathog,
6,
e1000821.
|
|
|
|
|
|
|
B.S.Thompson,
B.Moesker,
J.M.Smit,
J.Wilschut,
M.S.Diamond,
and
D.H.Fremont
(2009).
A therapeutic antibody against west nile virus neutralizes infection by blocking fusion within endosomes.
|
| |
PLoS Pathog,
5,
e1000453.
|
|
|
|
|
|
|
C.Sánchez-San Martín,
C.Y.Liu,
and
M.Kielian
(2009).
Dealing with low pH: entry and exit of alphaviruses and flaviviruses.
|
| |
Trends Microbiol,
17,
514-521.
|
|
|
|
|
|
|
D.E.Volk,
F.J.May,
S.H.Gandham,
A.Anderson,
J.J.Von Lindern,
D.W.Beasley,
A.D.Barrett,
and
D.G.Gorenstein
(2009).
Structure of yellow fever virus envelope protein domain III.
|
| |
Virology,
394,
12-18.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
D.M.Chisenhall,
and
C.N.Mores
(2009).
Diversification of West Nile virus in a subtropical region.
|
| |
Virol J,
6,
106.
|
|
|
|
|
|
|
E.Mehlhop,
S.Nelson,
C.A.Jost,
S.Gorlatov,
S.Johnson,
D.H.Fremont,
M.S.Diamond,
and
T.C.Pierson
(2009).
Complement protein C1q reduces the stoichiometric threshold for antibody-mediated neutralization of West Nile virus.
|
| |
Cell Host Microbe,
6,
381-391.
|
|
|
|
|
|
|
I.M.Yu,
H.A.Holdaway,
P.R.Chipman,
R.J.Kuhn,
M.G.Rossmann,
and
J.Chen
(2009).
Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion.
|
| |
J Virol,
83,
12101-12107.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.R.Vogt,
B.Moesker,
J.Goudsmit,
M.Jongeneelen,
S.K.Austin,
T.Oliphant,
S.Nelson,
T.C.Pierson,
J.Wilschut,
M.Throsby,
and
M.S.Diamond
(2009).
Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step.
|
| |
J Virol,
83,
6494-6507.
|
|
|
|
|
|
|
M.S.Diamond
(2009).
Progress on the development of therapeutics against West Nile virus.
|
| |
Antiviral Res,
83,
214-227.
|
|
|
|
|
|
|
M.V.Cherrier,
B.Kaufmann,
G.E.Nybakken,
S.M.Lok,
J.T.Warren,
B.R.Chen,
C.A.Nelson,
V.A.Kostyuchenko,
H.A.Holdaway,
P.R.Chipman,
R.J.Kuhn,
M.S.Diamond,
M.G.Rossmann,
and
D.H.Fremont
(2009).
Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody.
|
| |
EMBO J,
28,
3269-3276.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
N.Bonafé,
J.A.Rininger,
R.G.Chubet,
H.G.Foellmer,
S.Fader,
J.F.Anderson,
S.L.Bushmich,
K.Anthony,
M.Ledizet,
E.Fikrig,
R.A.Koski,
and
P.Kaplan
(2009).
A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells.
|
| |
Vaccine,
27,
213-222.
|
|
|
|
|
|
|
Q.Y.Wang,
S.J.Patel,
E.Vangrevelinghe,
H.Y.Xu,
R.Rao,
D.Jaber,
W.Schul,
F.Gu,
O.Heudi,
N.L.Ma,
M.K.Poh,
W.Y.Phong,
T.H.Keller,
E.Jacoby,
and
S.G.Vasudevan
(2009).
A small-molecule dengue virus entry inhibitor.
|
| |
Antimicrob Agents Chemother,
53,
1823-1831.
|
|
|
|
|
|
|
R.Rajamanonmani,
C.Nkenfou,
P.Clancy,
Y.H.Yau,
S.G.Shochat,
S.Sukupolvi-Petty,
W.Schul,
M.S.Diamond,
S.G.Vasudevan,
and
J.Lescar
(2009).
On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes.
|
| |
J Gen Virol,
90,
799-809.
|
|
|
|
|
|
|
R.Yennamalli,
N.Subbarao,
T.Kampmann,
R.P.McGeary,
P.R.Young,
and
B.Kobe
(2009).
Identification of novel target sites and an inhibitor of the dengue virus E protein.
|
| |
J Comput Aided Mol Des,
23,
333-341.
|
|
|
|
|
|
|
S.Kiermayr,
K.Stiasny,
and
F.X.Heinz
(2009).
Impact of quaternary organization on the antigenic structure of the tick-borne encephalitis virus envelope glycoprotein E.
|
| |
J Virol,
83,
8482-8491.
|
|
|
|
|
|
|
S.Nelson,
S.Poddar,
T.Y.Lin,
and
T.C.Pierson
(2009).
Protonation of individual histidine residues is not required for the pH-dependent entry of west nile virus: evaluation of the "histidine switch" hypothesis.
|
| |
J Virol,
83,
12631-12635.
|
|
|
|
|
|
|
V.Nayak,
M.Dessau,
K.Kucera,
K.Anthony,
M.Ledizet,
and
Y.Modis
(2009).
Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion.
|
| |
J Virol,
83,
4338-4344.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
W.M.Wahala,
A.A.Kraus,
L.B.Haymore,
M.A.Accavitti-Loper,
and
A.M.de Silva
(2009).
Dengue virus neutralization by human immune sera: role of envelope protein domain III-reactive antibody.
|
| |
Virology,
392,
103-113.
|
|
|
|
|
|
|
A.Pereboev,
V.Borisevich,
G.Tsuladze,
M.Shakhmatov,
D.Hudman,
E.Kazachinskaia,
I.Razumov,
V.Svyatchenko,
V.Loktev,
and
V.Yamshchikov
(2008).
Genetically delivered antibody protects against West Nile virus.
|
| |
Antiviral Res,
77,
6.
|
|
|
|
|
|
|
C.Sánchez-San Martín,
H.Sosa,
and
M.Kielian
(2008).
A stable prefusion intermediate of the alphavirus fusion protein reveals critical features of class II membrane fusion.
|
| |
Cell Host Microbe,
4,
600-608.
|
|
|
|
|
|
|
D.E.Volk,
K.M.Anderson,
S.H.Gandham,
F.J.May,
L.Li,
D.W.Beasley,
A.D.Barrett,
and
D.G.Gorenstein
(2008).
NMR assignments of the sylvatic dengue 1 virus envelope protein domain III.
|
| |
Biomol NMR Assign,
2,
155-157.
|
|
|
|
|
|
|
I.M.Yu,
W.Zhang,
H.A.Holdaway,
L.Li,
V.A.Kostyuchenko,
P.R.Chipman,
R.J.Kuhn,
M.G.Rossmann,
and
J.Chen
(2008).
Structure of the immature dengue virus at low pH primes proteolytic maturation.
|
| |
Science,
319,
1834-1837.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.S.Diamond,
T.C.Pierson,
and
D.H.Fremont
(2008).
The structural immunology of antibody protection against West Nile virus.
|
| |
Immunol Rev,
225,
212-225.
|
|
|
|
|
|
|
M.V.Bogachek,
E.V.Protopopova,
V.B.Loktev,
B.N.Zaitsev,
M.Favre,
S.K.Sekatskii,
and
G.Dietler
(2008).
Immunochemical and single molecule force spectroscopy studies of specific interaction between the laminin binding protein and the West Nile virus surface glycoprotein E domain II.
|
| |
J Mol Recognit,
21,
55-62.
|
|
|
|
|
|
|
R.Fritz,
K.Stiasny,
and
F.X.Heinz
(2008).
Identification of specific histidines as pH sensors in flavivirus membrane fusion.
|
| |
J Cell Biol,
183,
353-361.
|
|
|
|
|
|
|
R.Perera,
M.Khaliq,
and
R.J.Kuhn
(2008).
Closing the door on flaviviruses: entry as a target for antiviral drug design.
|
| |
Antiviral Res,
80,
11-22.
|
|
|
|
|
|
|
T.C.Pierson,
and
M.S.Diamond
(2008).
Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection.
|
| |
Expert Rev Mol Med,
10,
e12.
|
|
|
|
|
|
|
C.B.Whitehurst,
E.J.Soderblom,
M.L.West,
R.Hernandez,
M.B.Goshe,
and
D.T.Brown
(2007).
Location and role of free cysteinyl residues in the Sindbis virus E1 and E2 glycoproteins.
|
| |
J Virol,
81,
6231-6240.
|
|
|
|
|
|
|
D.E.Volk,
Y.C.Lee,
X.Li,
V.Thiviyanathan,
G.D.Gromowski,
L.Li,
A.R.Lamb,
D.W.Beasley,
A.D.Barrett,
and
D.G.Gorenstein
(2007).
Solution structure of the envelope protein domain III of dengue-4 virus.
|
| |
Virology,
364,
147-154.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.Ren,
T.Ding,
W.Zhang,
J.Song,
and
W.Ma
(2007).
Does Japanese encephalitis virus share the same cellular receptor with other mosquito-borne flaviviruses on the C6/36 mosquito cells?
|
| |
Virol J,
4,
83.
|
|
|
|
|
|
|
J.T.Huiskonen,
and
S.J.Butcher
(2007).
Membrane-containing viruses with icosahedrally symmetric capsids.
|
| |
Curr Opin Struct Biol,
17,
229-236.
|
|
|
|
|
|
|
K.Stiasny,
S.Brandler,
C.Kössl,
and
F.X.Heinz
(2007).
Probing the flavivirus membrane fusion mechanism by using monoclonal antibodies.
|
| |
J Virol,
81,
11526-11531.
|
|
|
|
|
|
|
M.Ledizet,
K.Kar,
H.G.Foellmer,
N.Bonafé,
K.G.Anthony,
L.H.Gould,
S.L.Bushmich,
E.Fikrig,
and
R.A.Koski
(2007).
Antibodies targeting linear determinants of the envelope protein protect mice against West Nile virus.
|
| |
J Infect Dis,
196,
1741-1748.
|
|
|
|
|
|
|
M.Throsby,
J.Ter Meulen,
C.Geuijen,
J.Goudsmit,
and
J.de Kruif
(2007).
Mapping and analysis of West Nile virus-specific monoclonal antibodies: prospects for vaccine development.
|
| |
Expert Rev Vaccines,
6,
183-191.
|
|
|
|
|
|
|
S.Sukupolvi-Petty,
S.K.Austin,
W.E.Purtha,
T.Oliphant,
G.E.Nybakken,
J.J.Schlesinger,
J.T.Roehrig,
G.D.Gromowski,
A.D.Barrett,
D.H.Fremont,
and
M.S.Diamond
(2007).
Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes.
|
| |
J Virol,
81,
12816-12826.
|
|
|
|
|
|
|
T.C.Pierson,
Q.Xu,
S.Nelson,
T.Oliphant,
G.E.Nybakken,
D.H.Fremont,
and
M.S.Diamond
(2007).
The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection.
|
| |
Cell Host Microbe,
1,
135-145.
|
|
|
|
|
|
|
T.Oliphant,
G.E.Nybakken,
S.K.Austin,
Q.Xu,
J.Bramson,
M.Loeb,
M.Throsby,
D.H.Fremont,
T.C.Pierson,
and
M.S.Diamond
(2007).
Induction of epitope-specific neutralizing antibodies against West Nile virus.
|
| |
J Virol,
81,
11828-11839.
|
|
|
|
|
|
|
Y.Zhang,
B.Kaufmann,
P.R.Chipman,
R.J.Kuhn,
and
M.G.Rossmann
(2007).
Structure of immature West Nile virus.
|
| |
J Virol,
81,
6141-6145.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
T.Oliphant,
G.E.Nybakken,
M.Engle,
Q.Xu,
C.A.Nelson,
S.Sukupolvi-Petty,
A.Marri,
B.E.Lachmi,
U.Olshevsky,
D.H.Fremont,
T.C.Pierson,
and
M.S.Diamond
(2006).
Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein.
|
| |
J Virol,
80,
12149-12159.
|
|
|
|
|
|
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.
|
|
Links
