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

• DOI: 10.7554/elife.50576
• Publication Date: 2019-12-19T13:00:14Z
• Authors: Wenchang Zhou; Giacomo Fiorin; Claudio Anselmi; Hossein Ali Karim...; Horacio Poblete; Lucy R Forrest; José D Faraldo-Gómez
• Keywords: Neurotransmitter transporter

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