NMR structures of fusion peptide from influenza hemagglutinin H3 subtype and its mutants
Article first published online: 12 FEB 2014
Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 20, Issue 4, pages 292–297, April 2014
How to Cite
Du, T., Jiang, L. and Liu, M. (2014), NMR structures of fusion peptide from influenza hemagglutinin H3 subtype and its mutants. J. Peptide Sci., 20: 292–297. doi: 10.1002/psc.2616
- Issue published online: 12 MAR 2014
- Article first published online: 12 FEB 2014
- Manuscript Accepted: 13 JAN 2014
- Manuscript Revised: 20 DEC 2013
- Manuscript Received: 16 SEP 2013
- National Basic Research Program of China. Grant Number: 2009CB918600
- National Natural Science Foundation of China. Grant Number: NSFC 21173257
- influenza fusion peptide;
The influenza fusion peptide located at the N-terminus of the hemagglutinin HA2 subunit initiates the fusing process of the viral membrane with the host cell endosomal membrane. It had been reported that the structure of a 20-residue H3 subtype fusion peptide (H3-HAfp20) was significantly different with that of a H1 subtype 23-residue one (H1-HAfp23). The sequential difference between the 12th and 15th residues of H1 and H3 subtypes could not fully explain the conformational variation. The first and last three amino acids of H3-HAfp23 involved in formation of hydrogen bonds may play an important role in fusion process. To confirm this hypothesis, we investigate the structures of H3-HAfp23 peptide and its mutants, G1S and G1V, in dodecylphosphatidyl choline micelles by using heteronuclear NMR technology. The results demonstrate that, similar to H1-HAfp23 but significantly different with H3-HAfp20, H3-HAfp23 also has tight helical hairpin structure with the N- and C-terminuses linked together because of the hydrogen bonds between Gly1 and the last three amino acids, Trp21―Tyr22―Gly23. Although the ‘hemifusion’ G1S and lethal G1V mutants have hairpin-like helical structures, the distances between the N- and C-terminuses are increased as shortage of the hydrogen bonds and the larger kink angle between the antiparallel helices. The paramagnetic ion titration experiments show that the terminuses are inserted into the dodecylphosphatidyl choline micelles used as solving media. These may imply that the tight helical hairpin structure, especially the closed conformation at terminus, plays an important role in fusion activity. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.