6MJH

The S31N mutant of the influenza A M2 proton channel in two distinct conformational states

6MJH の概要

• エントリーDOI: 10.2210/pdb6mjh/pdb
• 分子名称: Matrix protein 2, CALCIUM ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: viral protein, proton channel, s31n, membrane protein
• 由来する生物種: Influenza A virus (A/pigeon/Jiangsu/K23/2013(H9N2))
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 22446.69

構造登録者

Thomaston, J.L.,DeGrado, W.F. (登録日: 2018-09-20, 公開日: 2019-06-26, 最終更新日: 2024-11-06)

主引用文献

Thomaston, J.L.,Wu, Y.,Polizzi, N.,Liu, L.,Wang, J.,DeGrado, W.F.
X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case.
J.Am.Chem.Soc., 141:11481-11488, 2019

PubMed 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 Inward conformation, the mutant Asn31 side chain faces the channel pore and sterically blocks the adamantane binding site. In the Inward 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.

PubMed: 31184871
DOI: 10.1021/jacs.9b02196

実験手法

X-RAY DIFFRACTION (2.06 Å)