PDBsum entry 2wrf

Viral protein

PDB id: 2wrf

Contents

Protein chains

(+ 3 more) 486 a.a. *

Ligands

GAL-SIA

SIA

* Residue conservation analysis

PDB id:

2wrf

Name:

Viral protein

Title:

Structure of h2 avian jena hemagglutinin with human receptor

Structure:

Hemagglutinin. Chain: a, b, c, d, e, f, g, h, i. Fragment: residues 1-507

Source:

Influenza a virus (a/chicken/potsdam/4705/1984(h2n2)). Organism_taxid: 139280

Resolution:

3.10Å R-factor: 0.277 R-free: 0.337

Authors:

J.Liu,D.J.Stevens,L.F.Haire,P.A.Walker,P.J.Coombs,R.J.Russell, S.J.Gamblin,J.J.Skehel

Key ref:

J.Liu et al. (2009). Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957. Proc Natl Acad Sci U S A, 106, 17175-17180. PubMed id: 19805083 DOI: 10.1073/pnas.0906849106

Date:

01-Sep-09 Release date: 29-Sep-09

Protein chains

Q67326  (Q67326_9INFA) -  Hemagglutinin from Influenza A virus

Seq: 562 a.a.

Struc: 486 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1073/pnas.0906849106

Proc Natl Acad Sci U S A 106:17175-17180 (2009)

PubMed id: 19805083

Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957.

J.Liu, D.J.Stevens, L.F.Haire, P.A.Walker, P.J.Coombs, R.J.Russell, S.J.Gamblin, J.J.Skehel.

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.

Selected figure(s)

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.

Figures were selected by an automated process.