Protein Motifs for Proton Transfers That Build the Transmembrane Proton Gradient

Abstract

Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome c oxidase (CcO), are reviewed. These proteins all use water filled proton transfer paths. The proton pumps, that move protons uphill from low to high concentration compartments, also utilize Proton Loading Sites (PLS), that transiently load and unload protons and gates, which block backflow of protons. PLS and gates should be synchronized so PLS proton affinity is high when the gate opens to the side with few protons and low when the path is open to the high concentration side. Proton transfer paths in the proteins we describe have different design features. Linear paths are seen with a unique entry and exit and a relatively straight path between them. Alternatively, paths can be complex with a tangle of possible routes. Likewise, PLS can be a single residue that changes protonation state or a cluster of residues with multiple charge and tautomer states.

Common mechanism of activated catalysis in P-loop fold nucleoside triphosphatases -in varietate concordia

“…Mutations of either Glu-L212, or Asp-L213, or Ser-L223 block proton transfer from the surface [228, 233, 234]. For further details, see [216, 225, 235–237].…”

“…However, direct tracing of intra-protein displacements of protons in energy converting enzymes and chemical models (see [199,200,[207][208][209][210][211][212][213][214][215][216][217][218][219] for reviews) showed that fast proton transfer over a distance of up to 20 Å can be mediated by water bridges, provided that the distance between the groups involved is ≤ 3.0 Å, in accordance with Eigen [200]. Thereby it does not matter that water molecules are equally poor proton acceptors (with pKb of 0.0) and proton donors (with pKa of 14.0) because protons pass water by so-called von Grotthuss mechanism [220][221][222].…”

“…Mutations of either Glu-L212, or Asp-L213, or Ser-L223 block proton transfer from the surface [228,233,234]. For further details, see [216,225,[235][236][237]. B, a high-pK proton trap in bacteriorhodopsin (BR), a membrane protein that pumps a proton across the membrane in response to the photoexcitation of its retinal pigment, see [209,210,238,239] for reviews.…”

Characterizing Protein Protonation Microstates Using Monte Carlo Sampling

“…The ensemble of protein conformations broadens the distribution of protonation microstates since the residue proton affinity shifts as they sample different environments. Protonation states also change when ligands are bound , or when redox reactions occur at bound cofactors. , Proton pumps move protons through membrane embedded proteins as changes in protein conformation and redox states modify residue proton affinity. − As with the protein conformational states, some protonation microstates are essential for protein function while others simply result from multiple microstates being close in energy.…”

Characterizing protein protonation microstates using Monte Carlo sampling

“…Protonation states also change when ligands are bound 2,3 or when redox reactions occur at bound cofactors 7,8 . Proton pumps move protons through membrane embedded proteins as changes in protein conformation and redox states modify residue proton affinity [9][10][11][12][13] . As with the protein conformational states, some protonation microstates are essential for protein function while others simply result from multiple microstates being close in energy.…”