Structural highlights
Function
[Q9YP62_9INFA] Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation (By similarity).[SAAS:SAAS002089_004_400258]
Publication Abstract from PubMed
Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine.
Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus.,Hu J, Asbury T, Achuthan S, Li C, Bertram R, Quine JR, Fu R, Cross TA Biophys J. 2007 Jun 15;92(12):4335-43. Epub 2007 Mar 23. PMID:17384070[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hu J, Asbury T, Achuthan S, Li C, Bertram R, Quine JR, Fu R, Cross TA. Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus. Biophys J. 2007 Jun 15;92(12):4335-43. Epub 2007 Mar 23. PMID:17384070 doi:biophysj.106.090183
