Interplay between the electrostatic membrane potential and conformational changes in membrane proteins

Abstract

Transmembrane electrostatic membrane potential is a major energy source of the cell. Importantly, it determines the structure as well as function of charge‐carrying membrane proteins. Here, we discuss the relationship between membrane potential and membrane proteins, in particular whether the conformation of these proteins is integrally connected to the membrane potential. Together, these concepts provide a framework for rationalizing the types of conformational changes that have been observed in membrane proteins and for better understanding the electrostatic effects of the membrane potential on both reversible as well as unidirectional dynamic processes of membrane proteins.

P-type ATPases use a domain-association mechanism to couple ATP hydrolysis to conformational change

“…Interestingly, the interaction between the Trp residues and surrounding lipids are not mediated by hydrogen bonds with the polar head groups (Norimatsu et al 2017), in contrast to what is often assumed. It is likely that Trp residues exert their stabilizing effect on membrane proteins through interactions between the intrinsic (and induced) electric dipoles of their indole sidechains and the strong local electric field from the head-group phosphates of the surrounding lipid molecules (Zhang and Li 2019).…”

“…Similar amphipathic helices have been found in several major families of membrane proteins, including secondary active transporters, The mechanism of P-type ATPases coupling ATP hydrolysis ATP-binding cassette (ABC) exporters (Zhang et al 2018a), G-protein coupled receptors (GPCRs) (Zhang et al 2014), and voltage-gated ion channels (VGICs) (Zhang et al 2018b). Similar to the Trp and basic residues near the membrane surface, these amphipathic helices are likely to play important roles in restricting the mode of conformational changes of their connected TM-helix termini to sliding-only on the membrane surface (Zhang and Li 2019).…”

“…Consequently, not all of the four acidic residues may get protonated, and less positive charges from the counter ions than that of the substrate ions will be imported into the cytosol. It is reasonable to speculate that the structural and/or electrostatic effect of ±1 unit of electric charges in the substrate-binding pocket, which is located in the N TM -C TM interface, can propagate to the interfaces between the cytosolic domains (Zhang and Li 2019). Therefore, in the following discussion, we simplify all movement of substrate and counter ions as an efflux of one effective cation (Fig.…”

Towards understanding the mechanisms of proton pumps in Complex-I of the respiratory chain

“…Therefore, excitation of the resting state by an ''extra'' electric charge (such as injection of an electron pair) can be treated as independent of other preexisting interactions, simplifying our analysis on the energy converting process. Previously, we proposed that the interaction between the electrostatic membrane potential (DW) and a charged ligand can drive the conformational transition essential for functions of membrane proteins (Zhang and Li 2019). In a PMF-driven secondary active transporter, for example, the electrostatic force exerted on a proton immersed in the electric field of DW (*100 mV, corresponding to an electric charge density of *0.02 e 0 per 1000 Å 2 ) is typically *5 pN (Zhang et al 2015).…”

“…For instance, the positive-inside and negative-outside charge distribution in each domain of the antiporter-like subunits and its associated overall electric dipole potentially contribute to the electrostatic interactions required for the conformational changes of the proton-pumping subunits. Moreover, two types of interactions have been described for DW-driven conformational changes of membrane proteins (Zhang and Li 2019). The first type of conformational change is caused by changes in electric charges of the protein, under the condition of constant external DW, as exemplified by the electrogenic secondary active transporters (Zhang et al 2018a).…”