PDBsum entry 2kxa

Viral protein, immune system

PDB id: 2kxa

Contents

Protein chain

24 a.a.

PDB id:

2kxa

Name:

Viral protein, immune system

Title:

The hemagglutinin fusion peptide (h1 subtype) at ph 7.4

Structure:

Haemagglutinin ha2 chain peptide. Chain: a. Fragment: residues 1 to 23 of ha2 subunit (unp residues 345-367). Engineered: yes

Source:

Influenza a virus. Organism_taxid: 83206. Strain: a/swine/scotland/410440/94(h1n2). Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

10 models

Authors:

J.L.Lorieau,J.M.Louis,A.Bax

Key ref:

J.L.Lorieau et al. (2010). The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface. Proc Natl Acad Sci U S A, 107, 11341-11346. PubMed id: 20534508

Date:

29-Apr-10 Release date: 23-Jun-10

Protein chain

Q9YTC2  (Q9YTC2_9INFA) -  Hemagglutinin from Influenza A virus

Seq: 566 a.a.

Struc: 24 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

Proc Natl Acad Sci U S A 107:11341-11346 (2010)

PubMed id: 20534508

The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface.

J.L.Lorieau, J.M.Louis, A.Bax.

ABSTRACT

All but five of the N-terminal 23 residues of the HA2 domain of the influenza virus glycoprotein hemagglutinin (HA) are strictly conserved across all 16 serotypes of HA genes. The structure and function of this HA2 fusion peptide (HAfp) continues to be the focus of extensive biophysical, computational, and functional analysis, but most of these analyses are of peptides that do not include the strictly conserved residues Trp(21)-Tyr(22)-Gly(23). The heteronuclear triple resonance NMR study reported here of full length HAfp of sero subtype H1, solubilized in dodecylphosphatidyl choline, reveals a remarkably tight helical hairpin structure, with its N-terminal alpha-helix (Gly(1)-Gly(12)) packed tightly against its second alpha-helix (Trp(14)-Gly(23)), with six of the seven conserved Gly residues at the interhelical interface. The seventh conserved Gly residue in position 13 adopts a positive angle, enabling the hairpin turn that links the two helices. The structure is stabilized by multiple interhelical C(alpha)H to C=O hydrogen bonds, characterized by strong interhelical H(N)-H(alpha) and H(alpha)-H(alpha) NOE contacts. Many of the previously identified mutations that make HA2 nonfusogenic are also incompatible with the tight antiparallel hairpin arrangement of the HAfp helices.(15)N relaxation analysis indicates the structure to be highly ordered on the nanosecond time scale, and NOE analysis indicates HAfp is located at the water-lipid interface, with its hydrophobic surface facing the lipid environment, and the Gly-rich side of the helix-helix interface exposed to solvent.