X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case

Jessica L. Thomaston, Yibing Wu, Nicholas Polizzi, Lijun Liu, Jun Wang, William F. Degrado

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The amantadine-resistant S31N mutant of the influenza A M2 proton channel has become prevalent in currently circulating viruses. Here, we have solved an X-ray crystal structure of M2(22-46) S31N that contains two distinct conformational states within its asymmetric unit. This structure reveals the mechanism of adamantane resistance in both conformational states of the M2 channel. In the Inwardopen conformation, the mutant Asn31 side chain faces the channel pore and sterically blocks the adamantane binding site. In the Inwardclosed conformation, Asn31 forms hydrogen bonds with carbonyls at the monomer-monomer interface, which twists the monomer helices and constricts the channel pore at the drug binding site. We also examine M2(19-49) WT and S31N using solution NMR spectroscopy and show that distribution of the two conformational states is dependent on both detergent choice and experimental pH.

Original languageEnglish (US)
Pages (from-to)11481-11488
Number of pages8
JournalJournal of the American Chemical Society
Volume141
Issue number29
DOIs
StatePublished - Jul 24 2019

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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