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Title: XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction

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 open 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 conductionmore » cycle. The number of ordered pore waters decreases at pH 6.5 and 8.0, where the Inward open state is less stable. Furthermore, these studies provide a graphical view of the response of water to a change in charge within a restricted channel environment.« less

Authors:
 [1]; ORCiD logo [1]; ORCiD logo [2];  [3];  [3];  [4];  [5];  [1];  [6];  [1];  [7];  [3];  [3];  [8];  [9];  [3];  [5];  [3];  [2];  [10] more »;  [10];  [3];  [8];  [4]; ORCiD logo [1];  [1] « less
  1. Univ. of California, San Francisco, CA (United States)
  2. The Univ. of Tokyo, Tokyo (Japan)
  3. RIKEN SPring-8 Center, Saitama (Japan)
  4. High Energy Accelerator Research Organization (KEK), Ibaraki (Japan)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  6. Cornell Univ., Ithaca, NY (United States)
  7. Stanford Univ., Stanford, CA (United States); Stanford Univ., Palo Alto, CA (United States)
  8. RIKEN SPring-8 Center, Saitama (Japan); Kyoto Univ., Kyoto (Japan)
  9. RIKEN SPring-8 Center, Saitama (Japan); Osaka Univ., Osaka (Japan)
  10. Japan Synchrotron Radiation Research Institute, Hyogo (Japan)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1376273
Alternate Identifier(s):
OSTI ID: 1417656; OSTI ID: 1439226
Grant/Contract Number:  
GM122603; GM117593; OD009180; GM110580; STC-1231306; GRFP; 1S10RR027234-01; AC02-76SF00515; GM117126; AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 51; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; XFEL; proton channel; influenza; membrane protein

Citation Formats

Thomaston, Jessica L., Woldeyes, Rahel A., Nakane, Takanori, Yamashita, Ayumi, Tanaka, Tomoyuki, Koiwai, Kotaro, Brewster, Aaron S., Barad, Benjamin A., Chen, Yujie, Lemmin, Thomas, Uervirojnangkoorn, Monarin, Arima, Toshi, Kobayashi, Jun, Masuda, Tetsuya, Suzuki, Mamoru, Sugahara, Michihiro, Sauter, Nicholas K., Tanaka, Rie, Nureki, Osamu, Tono, Kensuke, Joti, Yasumasa, Nango, Eriko, Iwata, So, Yumoto, Fumiaki, Fraser, James S., and DeGrado, William F. XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction. United States: N. p., 2017. Web. doi:10.1073/pnas.1705624114.
Thomaston, Jessica L., Woldeyes, Rahel A., Nakane, Takanori, Yamashita, Ayumi, Tanaka, Tomoyuki, Koiwai, Kotaro, Brewster, Aaron S., Barad, Benjamin A., Chen, Yujie, Lemmin, Thomas, Uervirojnangkoorn, Monarin, Arima, Toshi, Kobayashi, Jun, Masuda, Tetsuya, Suzuki, Mamoru, Sugahara, Michihiro, Sauter, Nicholas K., Tanaka, Rie, Nureki, Osamu, Tono, Kensuke, Joti, Yasumasa, Nango, Eriko, Iwata, So, Yumoto, Fumiaki, Fraser, James S., & DeGrado, William F. XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction. United States. doi:10.1073/pnas.1705624114.
Thomaston, Jessica L., Woldeyes, Rahel A., Nakane, Takanori, Yamashita, Ayumi, Tanaka, Tomoyuki, Koiwai, Kotaro, Brewster, Aaron S., Barad, Benjamin A., Chen, Yujie, Lemmin, Thomas, Uervirojnangkoorn, Monarin, Arima, Toshi, Kobayashi, Jun, Masuda, Tetsuya, Suzuki, Mamoru, Sugahara, Michihiro, Sauter, Nicholas K., Tanaka, Rie, Nureki, Osamu, Tono, Kensuke, Joti, Yasumasa, Nango, Eriko, Iwata, So, Yumoto, Fumiaki, Fraser, James S., and DeGrado, William F. Wed . "XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction". United States. doi:10.1073/pnas.1705624114.
@article{osti_1376273,
title = {XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction},
author = {Thomaston, Jessica L. and Woldeyes, Rahel A. and Nakane, Takanori and Yamashita, Ayumi and Tanaka, Tomoyuki and Koiwai, Kotaro and Brewster, Aaron S. and Barad, Benjamin A. and Chen, Yujie and Lemmin, Thomas and Uervirojnangkoorn, Monarin and Arima, Toshi and Kobayashi, Jun and Masuda, Tetsuya and Suzuki, Mamoru and Sugahara, Michihiro and Sauter, Nicholas K. and Tanaka, Rie and Nureki, Osamu and Tono, Kensuke and Joti, Yasumasa and Nango, Eriko and Iwata, So and Yumoto, Fumiaki and Fraser, James S. and DeGrado, William F.},
abstractNote = {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 Inwardopen 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 Inwardopen state is less stable. Furthermore, these studies provide a graphical view of the response of water to a change in charge within a restricted channel environment.},
doi = {10.1073/pnas.1705624114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 51,
volume = 114,
place = {United States},
year = {2017},
month = {8}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1705624114

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Cited by: 7 works
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