Transient water wires mediate selective proton transport in designed channel proteins.

Autor: Kratochvil HT; Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA, USA. huong.kratochvil@unc.edu.; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. huong.kratochvil@unc.edu., Watkins LC; Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics and James Franck Institute, The University of Chicago, Chicago, IL, USA.; Kemper Insurance, Chicago, IL, USA., Mravic M; Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA, USA.; Department of Integrative Structural and Computational Biology Scripps Research Institute, La Jolla, CA, USA., Thomaston JL; Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA, USA., Nicoludis JM; Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA, USA.; Genentech, San Francisco, CA, USA., Somberg NH; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., Liu L; DLX Scientific, Lawrence, KS, USA., Hong M; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA., Voth GA; Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics and James Franck Institute, The University of Chicago, Chicago, IL, USA. gavoth@uchicago.edu., DeGrado WF; Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA, USA. william.degrado@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature chemistry [Nat Chem] 2023 Jul; Vol. 15 (7), pp. 1012-1021. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1038/s41557-023-01210-4
Abstrakt: Selective proton transport through proteins is essential for forming and using proton gradients in cells. Protons are conducted along hydrogen-bonded 'wires' of water molecules and polar side chains, which, somewhat surprisingly, are often interrupted by dry apolar stretches in the conduction pathways, inferred from static protein structures. Here we hypothesize that protons are conducted through such dry spots by forming transient water wires, often highly correlated with the presence of the excess protons in the water wire. To test this hypothesis, we performed molecular dynamics simulations to design transmembrane channels with stable water pockets interspersed by apolar segments capable of forming flickering water wires. The minimalist designed channels conduct protons at rates similar to viral proton channels, and they are at least 10 6 -fold more selective for H + over Na + . These studies inform the mechanisms of biological proton conduction and the principles for engineering proton-conductive materials.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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