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PDBsum entry 2fk0
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Viral protein
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PDB id
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2fk0
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Contents |
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(+ 3 more)
322 a.a.
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(+ 3 more)
175 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure and receptor specificity of the hemagglutinin from an h5n1 influenza virus.
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Authors
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J.Stevens,
O.Blixt,
T.M.Tumpey,
J.K.Taubenberger,
J.C.Paulson,
I.A.Wilson.
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Ref.
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Science, 2006,
312,
404-410.
[DOI no: ]
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PubMed id
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Abstract
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The hemagglutinin (HA) structure at 2.9 angstrom resolution, from a highly
pathogenic Vietnamese H5N1 influenza virus, is more related to the 1918 and
other human H1 HAs than to a 1997 duck H5 HA. Glycan microarray analysis of this
Viet04 HA reveals an avian alpha2-3 sialic acid receptor binding preference.
Introduction of mutations that can convert H1 serotype HAs to human alpha2-6
receptor specificity only enhanced or reduced affinity for avian-type receptors.
However, mutations that can convert avian H2 and H3 HAs to human receptor
specificity, when inserted onto the Viet04 H5 HA framework, permitted binding to
a natural human alpha2-6 glycan, which suggests a path for this H5N1 virus to
gain a foothold in the human population.
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Figure 1.
Fig. 1. Crystal structure of Viet04 HA and comparison with 1918
human H1, duck H5, and 1968 human H3 HAs. (A) Overview of the
Viet04 trimer, represented as a ribbon diagram. For clarity,
each monomer has been colored differently. Carbohydrates
observed in the electron-density maps are colored orange, and
all the asparagines that make up a glycosylation site are
labeled. Only Glu20, Glu289, and Phe^154 are not labeled, as
these are on the back of the molecule. The location of the
receptor binding, cleavage, and basic patch sites are
highlighted only on one monomer. All the figures were generated
and rendered with the use of MacPymol (66). (B) Structural
comparison of the Viet04 monomer (olive) with duck H5 (orange)
and 1918 H1 (red) HAs. Structures were first superimposed on the
HA2 domain of Viet04 through the following residues: Viet04,
Gly1 to Pro160; 1918 H1 (PDB: 1rd8), Gly1 to Pro160;
H3(PDB:2hmg), Gly1 to Pro160; H5 (PDB: 1jsm [PDB]
), Gly1 to Pro160. Orientation of the overlay approximates to
the blue monomer in (A). (C) Superimposition of the two long
 -helices of HA2
for 1918 H1 (PDB: 1rd8), avian H5 (PDB: 1jsm [PDB]
), human H3 (PDB: 2hmg [PDB]
), and Viet04 reveal that the extended interhelical loop of
Viet04 is more similar to the 1918 H1 than to the existing avian
H5 structure. The side chain of Phe^63 is illustrated as an
example of the close proximity of the two structures.
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Figure 2.
Fig. 2. Antigenic variation in recent H5N1 viruses mapped onto
the Viet04 structure. (Left) Side view of the Viet04 structure
in which natural mutations identified by comparison of 2005 with
2004 isolates (23) are colored yellow; escape mutants (24, 25)
are blue; and those that overlap in both analyses are green. All
of the 2004 and 2005 strains have a new potential glycosylation
site at position 158 in the HA1 chain (orange). The receptor
binding site is highlighted with a red oval. (Right) Top view
looking down onto the globular membrane distal end of the trimer
around the RBD showing that the mutations mainly cluster around
the RBD.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
312,
404-410)
copyright 2006.
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