 |
PDBsum entry 6bkt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Viral protein
|
PDB id
|
|
|
|
6bkt
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-Binding site.
|
|
|
Authors
|
|
N.C.Wu,
A.J.Thompson,
J.Xie,
C.W.Lin,
C.M.Nycholat,
X.Zhu,
R.A.Lerner,
J.C.Paulson,
I.A.Wilson.
|
|
|
Ref.
|
|
Nat Commun, 2018,
9,
1264.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
The hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses
is critical for attachment to host cells, which imposes a functional constraint
on its natural evolution. On the other hand, being part of the major antigenic
sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the
immune system. From large-scale mutagenesis experiments, we here show that
several of the natural RBS substitutions become integrated into an extensive
epistatic network that prevents substitution reversion. X-ray structural
analysis reveals the mechanistic consequences as well as changes in the mode of
receptor binding. Further studies are necessary to elucidate whether such
entrenchment limits future options for immune escape or adversely affect
long-term viral fitness.
|
|
|
|
|
|
|
