Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex.
BACKGROUND
To study the organization and interaction with the fusion domain (or fusion peptide, FP) of the transmembrane domain (TMD) of influenza virus envelope glycoprotein for its role in membrane fusion which is also essential in the cellular trafficking of biomolecules and sperm-egg fusion.


RESULTS
The fluorescence and gel electrophoresis experiments revealed a tight self-assembly of TMD in the model membrane. A weak but non-random interaction between TMD and FP in the membrane was found. In the complex, the central TMD oligomer was packed by FP in an antiparallel fashion. FP insertion into the membrane was altered by binding to TMD. An infrared study exhibited an enhanced membrane perturbation by the complex formation. A model was built to illustrate the role of TMD in the late stages of influenza virus-mediated membrane fusion reaction.


CONCLUSIONS
The TMD oligomer anchors the fusion protein in the membrane with minimal destabilization to the membrane. Upon associating with FP, the complex exerts a synergistic effect on the membrane perturbation. This effect is likely to contribute to the complete membrane fusion during the late phase of fusion protein-induced fusion cascade. The results presented in the work characterize the nature of the interaction of TMD with the membrane and TMD in a complex with FP in the steps leading to pore initiation and dilation during virus-induced fusion. Our data and proposed fusion model highlight the key role of TMD-FP interaction and have implications on the fusion reaction mediated by other type I viral fusion proteins. Understanding the molecular mechanism of membrane fusion may assist in the design of anti-viral drugs.
Chang
Ding-Kwo
DK
Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, Republic of China. dkc@chem.sinica.edu.tw
Cheng
Shu-Fang
SF
Kantchev
Eric Aseen B
EA
Lin
Chi-Hui
CH
Liu
Yu-Tsan
YT
D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008561:Membrane Fusion; D017433:Protein Structure, Secondary; D012235:Rhodamines; D013050:Spectrometry, Fluorescence; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008051:Lipid Bilayers; D012235:Rhodamines; D014760:Viral Fusion Proteins