2KWX

The V27A mutant of influenza A M2 proton channel

2KWX の概要

• エントリーDOI: 10.2210/pdb2kwx/pdb
• 関連するPDBエントリー: 2KIH 2RLF
• 分子名称: Matrix protein 2 (1 entity in total)
• 機能のキーワード: m2 proton channel, influenza a, v27a resistant mutant, transport protein
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane (By similarity): P63231
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 17681.17

構造登録者

Pielak, R.M.,Chou, J.J. (登録日: 2010-04-20, 公開日: 2010-09-29, 最終更新日: 2024-05-22)

主引用文献

Pielak, R.M.,Chou, J.J.
Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel.
Biochem.Biophys.Res.Commun., 401:58-63, 2010

PubMed Abstract: The M2 protein of influenza A virus forms a proton-selective channel that is required for viral replication. It is the target of the anti-influenza drugs, amantadine and rimantadine. Widespread drug resistant mutants, however, has greatly compromised the effectiveness of these drugs. Here, we report the solution NMR structure of the highly pathogenic, drug resistant mutant V27A. The structure reveals subtle structural differences from wildtype that maybe linked to drug resistance. The V27A mutation significantly decreases hydrophobic packing between the N-terminal ends of the transmembrane helices, which explains the looser, more dynamic tetrameric assembly. The weakened channel assembly can resist drug binding either by destabilizing the rimantadine-binding pocket at Asp44, in the case of the allosteric inhibition model, or by reducing hydrophobic contacts with amantadine in the pore, in the case of the pore-blocking model. Moreover, the V27A structure shows a substantially increased channel opening at the N-terminal end, which may explain the faster proton conduction observed for this mutant. Furthermore, due to the high quality NMR data recorded for the V27A mutant, we were able to determine the structured region connecting the channel domain to the C-terminal amphipathic helices that was not determined in the wildtype structure. The new structural data show that the amphipathic helices are packed much more closely to the channel domain and provide new insights into the proton transfer pathway.

PubMed: 20833142
DOI: 10.1016/j.bbrc.2010.09.008
主引用文献が同じPDBエントリー

実験手法

SOLUTION NMR