Format

Send to

Choose Destination
Elife. 2019 Dec 19;8. pii: e50576. doi: 10.7554/eLife.50576.

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

Author information

1
Theoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
2
Computational Structural Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.

Abstract

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.

KEYWORDS:

enhanced sampling; membrane morphology; membrane transport; molecular biophysics; molecular simulation; none; structural biology; thermodynamics

Conflict of interest statement

WZ, GF, CA, HK, HP No competing interests declared, LF Reviewing editor, eLife, JF Senior editor, eLife

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center