5TTC

XFEL structure of influenza A M2 wild type TM domain at high pH in the lipidic cubic phase at room temperature

5TTC の概要

• エントリーDOI: 10.2210/pdb5ttc/pdb
• 関連するPDBエントリー: 5JOO
• 分子名称: Matrix protein 2, CHLORIDE ION, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: xfel, influenza, proton channel, room temperature, membrane protein
• 由来する生物種: Influenza A virus (A/Hickox/1940(H1N1))
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2869.95

構造登録者

Thomaston, J.L.,Woldeyes, R.A.,Fraser, J.S.,DeGrado, W.F. (登録日: 2016-11-02, 公開日: 2017-08-23, 最終更新日: 2024-10-16)

主引用文献

Thomaston, J.L.,Woldeyes, R.A.,Nakane, T.,Yamashita, A.,Tanaka, T.,Koiwai, K.,Brewster, A.S.,Barad, B.A.,Chen, Y.,Lemmin, T.,Uervirojnangkoorn, M.,Arima, T.,Kobayashi, J.,Masuda, T.,Suzuki, M.,Sugahara, M.,Sauter, N.K.,Tanaka, R.,Nureki, O.,Tono, K.,Joti, Y.,Nango, E.,Iwata, S.,Yumoto, F.,Fraser, J.S.,DeGrado, W.F.
XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction.
Proc. Natl. Acad. Sci. U.S.A., 114:13357-13362, 2017

PubMed Abstract: The M2 proton channel of influenza A is a drug target that is essential for the reproduction of the flu virus. It is also a model system for the study of selective, unidirectional proton transport across a membrane. Ordered water molecules arranged in "wires" inside the channel pore have been proposed to play a role in both the conduction of protons to the four gating His37 residues and the stabilization of multiple positive charges within the channel. To visualize the solvent in the pore of the channel at room temperature while minimizing the effects of radiation damage, data were collected to a resolution of 1.4 Å using an X-ray free-electron laser (XFEL) at three different pH conditions: pH 5.5, pH 6.5, and pH 8.0. Data were collected on the Inward state, which is an intermediate that accumulates at high protonation of the His37 tetrad. At pH 5.5, a continuous hydrogen-bonded network of water molecules spans the vertical length of the channel, consistent with a Grotthuss mechanism model for proton transport to the His37 tetrad. This ordered solvent at pH 5.5 could act to stabilize the positive charges that build up on the gating His37 tetrad during the proton conduction cycle. The number of ordered pore waters decreases at pH 6.5 and 8.0, where the Inward state is less stable. These studies provide a graphical view of the response of water to a change in charge within a restricted channel environment.

PubMed: 28835537
DOI: 10.1073/pnas.1705624114

実験手法

X-RAY DIFFRACTION (1.4 Å)