Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Influenza A M2 Channel Oligomerization is Sensitive to its Chemical Environment Viroporins are small viral ion channels that play important roles in the viral infection cycle and are proven antiviral drug targets. Matrix protein 2 from influenza A (AM2) is the best characterized viroporin, and the current paradigm is that AM2 forms monodisperse tetramers. Here, we used native mass spectrometry and other techniques to characterize the oligomeric state of both the full-length and transmembrane domain (TM) of AM2 in a variety of different pH and detergent conditions. Unexpectedly, we discovered that AM2 formed a range of different oligomeric complexes that were strongly influenced by the local chemical environment. Native mass spectrometry of AM2 in nanodiscs with different lipids showed that lipids also affected the oligomeric states of AM2. Finally, nanodiscs uniquely enabled measurement of amantadine binding stoichiometries to AM2 in the intact lipid bilayer. These unexpected results reveal that AM2 can form a wider range of oligomeric states than previously thought possible, which may provide new potential mechanisms of influenza pathology and pharmacology.

Significance StatementMany viruses contain small ion channels called viroporins that play diverse roles in viral infections. Influenza A M2 (AM2) is the best characterized viroporin and the target of the antivirals amantadine and rimantadine. Although past structural studies showed AM2 was a monodisperse tetramer, we discovered that AM2 can form polydisperse and dynamic oligomers that are sensitive to their local chemical environment. Our findings provide a new perspective on the structure and mechanisms of AM2 that may extend to other viroporins.
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The categories of this paper are: ecology
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The categories of this paper are: microbiology
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The categories of this paper are: developmental
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The categories of this paper are: immunology
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The categories of this paper are: molecular
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The categories of this paper are: neuroscience
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The categories of this paper are: toxicology
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The categories of this paper are: and
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The categories of this paper are: epidemiology
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The categories of this paper are: education
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The categories of this paper are: synthetic
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The categories of this paper are: paleontology
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The categories of this paper are: biochemistry
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The categories of this paper are: cognition
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The categories of this paper are: pathology
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The categories of this paper are: bioengineering