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Structure of an analog of fusion peptide from hemagglutinin

Published online by Cambridge University Press:  01 April 2000

PETER V. DUBOVSKII
Affiliation:
Department of Molecular Science, Graduate School of Science and Technology, Kobe University, Kobe 657-8501, Japan Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow 117871, Russia
HUA LI
Affiliation:
Department of Molecular Science, Graduate School of Science and Technology, Kobe University, Kobe 657-8501, Japan
SHO TAKAHASHI
Affiliation:
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan
ALEXANDER S. ARSENIEV
Affiliation:
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow 117871, Russia
KAZUYUKI AKASAKA
Affiliation:
Department of Molecular Science, Graduate School of Science and Technology, Kobe University, Kobe 657-8501, Japan Department of Chemistry Faculty of Science, Kobe University, Kobe 657-8501, Japan
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Abstract

A 20-residue peptide E5 containing five glutamates, an analog of the fusion peptide of influenza virus hemagglutinin (HA) exhibiting fusion activity at acidic pH lower than 6.0–6.5 was studied by circular dichroism (CD), Fourier transform infrared, and 1H-NMR spectroscopy in water, water/trifluoroethanol (TFE) mixtures, dodecylphosphocholine (DPC) micelles, and phospholipid vesicles. E5 became structurally ordered at pH ≤6 and the helical content in the peptide increased in the row: water < water/TFE < DPC ∼ phospholipid vesicle while the amount of β-structure was approximately reverse. 1H-NMR data and line-broadening effect of 5-, 16-doxylstearates on proton resonances of DPC bound peptide showed E5 forms amphiphilic α-helix in residues 2–18, which is flexible in 11–18 part. The analysis of the proton chemical shifts of DPC bound and CD intensity at 220 nm of phospholipid bound E5 showed that the pH dependence of helical content is characterized by the same pKa ≈5.6. Only Glu11 and Glu15 in DPC bound peptide showed such elevated pKas, presumably due to transient hydrogen bond(s) Glu11 (Glu15) δCOO(H+) … HN Glu15 that dispose(s) the side chain of Glu11 (Glu15) residue(s) close to the micelle/water interface. These glutamates are present in the HA-fusion peptide and the experimental half-maximal pH of fusion for HA and E5 peptides is ∼5.6. Therefore, a specific anchorage of these peptides onto membrane necessary for fusion is likely driven by the protonation of the carboxylate group of Glu11 (Glu15) residue(s) participating in transient hydrogen bond(s).

Type
Research Article
Copyright
© 2000 The Protein Society

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