Mobility Measurements Probe Conformational Changes in Membrane Proteins due to Tension

TL;DR

This study shows how membrane tension affects the conformation of membrane proteins like KvAP by measuring their diffusion and membrane deformation, revealing significant structural changes and torsional stiffness.

Contribution

It introduces a method to infer conformational changes in membrane proteins from diffusion measurements influenced by membrane tension.

Findings

Membrane tension causes significant conformational changes in KvAP.

Diffusivity measurements can infer protein conformation changes.

Torsional stiffness of KvAP is approximately 26.8 kT.

Abstract

The function of membrane-embedded proteins such as ion channels depends crucially on their conformation. We demonstrate how conformational changes in asymmetric membrane proteins may be inferred from measurements of their diffusion. Such proteins cause local deformations in the membrane, which induce an extra hydrodynamic drag on the protein. Using membrane tension to control the magnitude of the deformations and hence the drag, measurements of diffusivity can be used to infer--- via an elastic model of the protein--- how conformation is changed by tension. Motivated by recent experimental results [Quemeneur et al., Proc. Natl. Acad. Sci. USA, 111 5083 (2014)] we focus on KvAP, a voltage-gated potassium channel. The conformation of KvAP is found to change considerably due to tension, with its `walls', where the protein meets the membrane, undergoing significant angular strains. The torsional stiffness is determined to be 26.8 kT at room temperature. This has implications for both the structure and function of such proteins in the environment of a tension-bearing membrane.