 |
PDBsum entry 2wrf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Viral protein
|
PDB id
|
|
|
|
2wrf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of receptor complexes formed by hemagglutinins from the asian influenza pandemic of 1957.
|
|
|
Authors
|
|
J.Liu,
D.J.Stevens,
L.F.Haire,
P.A.Walker,
P.J.Coombs,
R.J.Russell,
S.J.Gamblin,
J.J.Skehel.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2009,
106,
17175-17180.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
The viruses that caused the three influenza pandemics of the twentieth century
in 1918, 1957, and 1968 had distinct hemagglutinin receptor binding
glycoproteins that had evolved the capacity to recognize human cell receptors.
We have determined the structure of the H2 hemagglutinin from the second
pandemic, the "Asian Influenza" of 1957. We compare it with the 1918 "Spanish
Influenza" hemagglutinin, H1, and the 1968 "Hong Kong Influenza" hemagglutinin,
H3, and show that despite its close overall structural similarity to H1, and its
more distant relationship to H3, the H2 receptor binding site is closely related
to that of H3 hemagglutinin. By analyzing hemagglutinins of potential H2 avian
precursors of the pandemic virus, we show that the human receptor can be bound
by avian hemagglutinins that lack the human-specific mutations of H2 and H3
pandemic viruses, Gln-226Leu, and Gly-228Ser. We show how Gln-226 in the avian
H2 receptor binding site, together with Asn-186, form hydrogen bond networks
through bound water molecules to mediate binding to human receptor. We show that
the human receptor adopts a very similar conformation in both human and avian
hemagglutinin-receptor complexes. We also show that Leu-226 in the receptor
binding site of human virus hemagglutinins creates a hydrophobic environment
near the Sia-1-Gal-2 glycosidic linkage that favors binding of the human
receptor and is unfavorable for avian receptor binding. We consider the
significance for the development of pandemics, of the existence of avian viruses
that can bind to both avian and human receptors.
|
|
|
|
|
|
|
|
Figure 1.
Ribbons representation of different H2 HA monomers and
receptor binding sites. (A) Superposition of the monomers of two
human H2 HAs: A/Singapore/1/57 and A/Japan/305/57 colored green
and yellow respectively. (B) Three avian H2 HAs: A/ck/New
York/29878/91 colored gray, A/dk/Ontario/77 colored in blue and
A/ck/potsdam/4705/84 colored orange red. (C) Overlap of monomers
of a human H2 HA colored in green and avian H2 HA colored in
blue. The region highlighted by the gray ellipse at the top of
the panel shows the receptor binding domain, an expanded version
of which is shown in (D). Conserved residues such as Tyr-98,
Ser-136, Trp-153, and His-183 are shown in stick representation
together with other residues important in receptor binding
specificity such as Asn-186, Glu-190, and Leu-194, as well as
the Gln/Leu-226, Gly/Ser-228 pair.
|
|
Figure 3.
Overlap of the receptor binding domains of H1, H2, and H3 HAs
in complexes with receptor analogues. (A) The overlapped
receptor binding sites of human HAs for H1 A/S.Carolina/1918,
(blue), H2 A/Singapore/1/57, (yellow) and H3 A/Aichi/2/68, (22)
(gray) in complex with human receptor analogue, LSTc. (B) The
receptor binding domains of avian HAs for H1, A/dk/Alberta/76
(blue), H2, A/dk/Ontario/77 (yellow), and H3, A/dk/Ukraine/63
(25) (gray) in complex with human receptor analogue. The
sialopentasaccharides are colored according to the HAs to which
they are bound and some of the side-chains discussed in the text
are shown in stick representation.
|
|
|
|
|
|
|
|
|
|
