 |
PDBsum entry 1jsh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Viral protein
|
PDB id
|
|
|
|
1jsh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
X-Ray structures of h5 avian and h9 swine influenza virus hemagglutinins bound to avian and human receptor analogs.
|
|
|
Authors
|
|
Y.Ha,
D.J.Stevens,
J.J.Skehel,
D.C.Wiley.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2001,
98,
11181-11186.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The three-dimensional structures of avian H5 and swine H9 influenza
hemagglutinins (HAs) from viruses closely related to those that caused outbreaks
of human disease in Hong Kong in 1997 and 1999 were determined bound to avian
and human cell receptor analogs. Emerging influenza pandemics have been
accompanied by the evolution of receptor-binding specificity from the preference
of avian viruses for sialic acid receptors in alpha2,3 linkage to the preference
of human viruses for alpha2,6 linkages. The four new structures show that HA
binding sites specific for human receptors appear to be wider than those
preferring avian receptors and how avian and human receptors are distinguished
by atomic contacts at the glycosidic linkage. alpha2,3-Linked sialosides bind
the avian HA in a trans conformation to form an alpha2,3 linkage-specific motif,
made by the glycosidic oxygen and 4-OH of the penultimate galactose, that is
complementary to the hydrogen-bonding capacity of Gln-226, an avian-specific
residue. alpha2,6-Linked sialosides bind in a cis conformation, exposing the
glycosidic oxygen to solution and nonpolar atoms of the receptor to Leu-226, a
human-specific residue. The new structures are compared with previously reported
crystal structures of HA/sialoside complexes of the H3 subtype that caused the
1968 Hong Kong Influenza virus pandemic and analyzed in relation to HA sequences
of all 15 subtypes and to receptor affinity data to make clearer how
receptor-binding sites of HAs from avian viruses evolve as the virus adapts to
humans.
|
|
|
|
|
|
|
|
Figure 3.
Fig. 3. Atomic interactions between H5, H9, and H3 HAs
and sialosides. (a) Potential hydrogen bonds (dashed red)
between LSTc and the swine H9 HA. (b) Comparison of the binding
of LSTc (  2,6) with
the 1999 swine H9 (red) and 1968 human H3 (blue) subtype HA.
Purple circles, common contacts; blue, H3 contacts; red, H9
contacts. (c) Comparison of the binding of LSTa ( 2,3) with
the 1997 avian H5 (green), 1999 swine H9 (red), and 1968 human
H3 (blue) subtype HAs. Purple circles, common contacts; blue, H3
contacts; green, H5 contacts; red, H9 contacts.
|
|
Figure 4.
Fig. 4. Swine H9 and human H3 HA binding sites preferring
2,6
linkages are wider than avian H5 preferring 2,3. The H9
swine (gray), H3 human (green), and H5 avian (white) 226/228
loops are superimposed, showing that the H5 avian 220s loop
(Gln-226/Gly-228) is closer to the opposing 130s loop than the
H9 swine (Leu-226/Gly-228) or H3 human (Leu-226/Ser-228).
Contact between Ala-138 and the lower methyl group of Leu-226
requires a more "open" site. The glycosidic oxygen of sialic
acid (atom colors) is labeled with an asterisk. A water molecule
(red sphere) mediates interactions between the amide group of
Gly-228 and the 8- and 9-OHs of sialic acid in H9 swine and H5
avian HAs. The hydroxyl group of Ser-228 "replaces" the water
molecule to form a hydrogen bond with 9-OH in the H3 human HA.
|
|
|
|
|
|
|
|
|
|
