Proton Transfer via Protein Bound Water Molecules

Abstract

How protons migrate via protein-bound water molecules is becoming an emerging research-field in biology, ever since Grotthuss proposed the proton transfer along water chains in liquid water in physical-chemistry. High resolution three-dimensional crystal-structures in the protein ground states of proton- pumps and proton-channels revealed internal protein bound water molecules. Recent time-resolved FTIR measurements revealed their dynamics, especially the H-bond changes, and showed how such protein bound water molecules can be actively involved in proton transfer using the light-driven proton pump bacteriorhodopsin (bR) as model system [1]. In the first half of the pumping-cycle protons are released from the internal central proton-binding site to the extracellular site of the protein. The detailed proton transfer via such water molecules involves preordered dangling water, a strong hydrogen-bonded water and most interestingly, a protonated water complex as the proton release group, which we identified for the first time in a protein [2]. Such a protonated water-complex was identified before in liquid water and ice by Manfred Eigen and is called therefore Eigen-cation. In the second half of the pumping-cycle, the central binding site is reprotonated from Asp96 [1]. In contrast to the release site, the uptake site does not contain a pre-ordered water chain in the protein ground state. However, a transient water chain between asp 96 and the central binding site evolves in the hydrophobic part of the protein interior in an intermediate of the pumping-cycle on the milli-second time-scale. Thereby, the proton is transferred from asp 96 to the central binding site and the pump is reset [4]. In summary, the emerging paradigm invokes the principle that protein bound water molecules are as functional as amino acids residues [2,3]. A similar mechanism might apply in other proton transferringproteins such as the photosynthetic reaction-center or the optogenetic tool channelrhodops [5].The finding by Eigen in liquid water is now extended by our results from physical-chemistry in liquids to the life-science in proteins.