eLife (Dec 2019)

Large-scale state-dependent membrane remodeling by a transporter protein

  • Wenchang Zhou,
  • Giacomo Fiorin,
  • Claudio Anselmi,
  • Hossein Ali Karimi-Varzaneh,
  • Horacio Poblete,
  • Lucy R Forrest,
  • José D Faraldo-Gómez

DOI
https://doi.org/10.7554/eLife.50576
Journal volume & issue
Vol. 8

Abstract

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That channels and transporters can influence the membrane morphology is increasingly recognized. Less appreciated is that the extent and free-energy cost of these deformations likely varies among different functional states of a protein, and thus, that they might contribute significantly to defining its mechanism. We consider the trimeric Na+-aspartate symporter GltPh, a homolog of an important class of neurotransmitter transporters, whose mechanism entails one of the most drastic structural changes known. Molecular simulations indicate that when the protomers become inward-facing, they cause deep, long-ranged, and yet mutually-independent membrane deformations. Using a novel simulation methodology, we estimate that the free-energy cost of this membrane perturbation is in the order of 6–7 kcal/mol per protomer. Compensating free-energy contributions within the protein or its environment must thus stabilize this inward-facing conformation for the transporter to function. We discuss these striking results in the context of existing experimental observations for this and other transporters.

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