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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1]; ORCiD logo [2]; ORCiD logo [3];  [4];  [4];  [5];  [6];  [2];  [7];  [1];  [8];  [4];  [4];  [9];  [10];  [4];  [6];  [4];  [3];  [11] more »;  [11];  [4];  [12];  [5]; ORCiD logo [2];  [1] « less
  1. Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158,
  2. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158,
  3. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan,
  4. SPring-8 Angstrom Compact Free Electron Laser (SACLA) Science Research Group, RIKEN SPring-8 Center, Saitama 351-0198, Japan,
  5. Structural Biology Research Center, High Energy Accelerator Research Organization (KEK), Ibaraki 305-0801, Japan,
  6. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
  7. School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14853,
  8. Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305,, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305,, Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA 94304,, Department of Photon Science, Stanford University, Stanford, CA 94305,, Department of Structural Biology, Stanford University, Stanford, CA 94305,
  9. SPring-8 Angstrom Compact Free Electron Laser (SACLA) Science Research Group, RIKEN SPring-8 Center, Saitama 351-0198, Japan,, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan,
  10. SPring-8 Angstrom Compact Free Electron Laser (SACLA) Science Research Group, RIKEN SPring-8 Center, Saitama 351-0198, Japan,, Institute for Protein Research, Osaka University, Osaka 565-0871, Japan,
  11. Experimental Instrumentation Team, Japan Synchrotron Radiation Research Institute, Hyogo 679-5198, Japan,
  12. SPring-8 Angstrom Compact Free Electron Laser (SACLA) Science Research Group, RIKEN SPring-8 Center, Saitama 351-0198, Japan,, Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
+ Show Author Affiliations

TheM2 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 amembrane. 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 conduction cycle. The number of ordered pore waters decreases at pH 6.5 and 8.0, where the Inwardopen 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.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515; GM122603; GM117593; OD009180; GM110580; STC-1231306; GRFP; 1S10RR027234-01; GM117126; AC02-05CH11231
OSTI ID:
1376273
Alternate ID(s):
OSTI ID: 1417656; OSTI ID: 1439226
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 114 Journal Issue: 51; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 48 works
Citation information provided by
Web of Science

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
XFEL
proton channel
influenza
membrane protein