PDBsum entry 6bkt

Viral protein

PDB id: 6bkt

Contents

Protein chains

317 a.a.

173 a.a.

Ligands

NAG-NAG ×4

NAG-GAL-SIA

NAG ×3

PEG

SO4 ×4

1PE ×2

Waters ×474

PDB id:

6bkt

Name:

Viral protein

Title:

Crystal structure of the a/michigan/15/2014 (h3n2) influenza virus hemagglutinin in complex with 6'-sln

Structure:

Hemagglutinin. Chain: a. Engineered: yes. Hemagglutinin. Chain: b. Engineered: yes

Source:

Influenza a virus. A/michigan/15/2014(h3n2). Organism_taxid: 1731408. Gene: ha. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_taxid: 7111

Resolution:

1.80Å R-factor: 0.175 R-free: 0.200

Authors:

N.C.Wu,I.A.Wilson

Key ref:

N.C.Wu et al. (2018). A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site. Nat Commun, 9, 1264. PubMed id: 29593268

Date:

09-Nov-17 Release date: 28-Feb-18

Protein chain

A0A0Y0S9M3  (A0A0Y0S9M3_9INFA) -  Hemagglutinin from Influenza A virus

Seq: 566 a.a.

Struc: 317 a.a.*

Protein chain

A0A0N9RDU4  (A0A0N9RDU4_9INFA) -  Hemagglutinin from Influenza A virus

Seq: 566 a.a.

Struc: 173 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Nat Commun 9:1264 (2018)

PubMed id: 29593268

A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site.

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.

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.