Effects of alterations of the amino-terminal glycine of influenza hemagglutinin fusion peptide on its structure, organization and membrane interactions.
Mutations of the glycine residue at the amino terminus of HA2 have been shown to have a large effect on the fusion activity of HA2, the extent of which apparently correlates with the side chain bulkiness of the substituting amino acids. To investigate into the cause of abrogation in fusogenicity and virus-promoted fusion mechanism, we synthesized several peptides in which this glycine was substituted by serine, glutamic acid, or lysine. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl sn-glycero-3-phosphoglycerol (DMPG) were used as model membranes in the fluorescence, circular dichroism (CD), and FTIR measurements while sodium dodecyl sulfate was used in NMR studies. We found that, for the less active variants, affinity to membrane, degree of solvent dehydration, lipid perturbation, depth of insertion, and helicity were less. Comparison of affinity to membrane bilayer among these analogs revealed that binding of the fusion peptide is determined largely by the hydrophobic effect. Additionally, the orientation is closer to the membrane normal for the wild-type fusion peptide in the helix form while the inactive analogs inserted more parallel to the membrane surface.
Wu
Cheng-Wei
CW
Institute of Chemistry, Academia Sinica, 115, Taipei, Taiwan, ROC.
Cheng
Shu-Fang
SF
Huang
Wei-Ning
WN
Trivedi
Vishwa Deo
VD
Veeramuthu
Balakrishnan
B
Assen B
Kantchev
K
Wu
Wen-Guey
WG
Chang
Ding-Kwo
DK
D000595:Amino Acid Sequence; D005453:Fluorescence; D005998:Glycine; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000502:physiology; D006461:Hemolysis; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion; D008823:Micelles; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D008823:Micelles; D005998:Glycine