Abstract |
The fusion domain of the influenza coat protein hemagglutinin HA2, bound to dodecyl phosphocholine micelles, was recently shown to adopt a structure consisting of two antiparallel α-helices, packed in an exceptionally tight hairpin configuration. Four interhelical H(α) to C═O aliphatic H-bonds were identified as factors stabilizing this fold. Here, we report evidence for an additional stabilizing force: a strong charge-dipole interaction between the N-terminal Gly(1) amino group and the dipole moment of helix 2. pH titration of the amino-terminal (15)N resonance, using a methylene-TROSY-based 3D NMR experiment, and observation of Gly(1 13)C' show a strongly elevated pK = 8.8, considerably higher than expected for an N-terminal amino group in a lipophilic environment. Chemical shifts of three C-terminal carbonyl carbons of helix 2 titrate with the protonation state of Gly(1)-N, indicative of a close proximity between the N-terminal amino group and the axis of helix 2, providing an optimal charge-dipole stabilization of the antiparallel hairpin fold. pK values of the side-chain carboxylate groups of Glu(11) and Asp(19) are higher by about 1 and 0.5 unit, respectively, than commonly seen for solvent-exposed side chains in water-soluble proteins, indicative of dielectric constants of ε = ∼30 (Glu(11)) and ∼60 (Asp(19)), placing these groups in the headgroup region of the phospholipid micelle.
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Authors | Justin L Lorieau, John M Louis, Ad Bax |
Journal | Journal of the American Chemical Society
(J Am Chem Soc)
Vol. 133
Issue 9
Pg. 2824-7
(Mar 09 2011)
ISSN: 1520-5126 [Electronic] United States |
PMID | 21319795
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- Hemagglutinins, Viral
- Peptides
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Topics |
- Amino Acid Sequence
- Hemagglutinins, Viral
(chemistry)
- Humans
- Influenza A virus
(chemistry)
- Influenza, Human
(virology)
- Models, Molecular
- Nuclear Magnetic Resonance, Biomolecular
- Peptides
(chemistry)
- Protein Structure, Secondary
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