Biophysics of Membrane Protein Signaling

Main Text

Membrane proteins such as G protein-coupled receptors, channels, and transporters, as well as variations in the membrane composition itself, drive signaling across cellular membranes. These processes are key for cells to sense their environment, store energy, and respond to stimuli. There has been a significant leap in our understanding of membrane proteins in the last two decades through the deployment of novel biophysical tools at the molecular and cellular level, and an explosion of structural insights from crystallography and cryoelectron microscopy. This special issue of Biophysical Journal on membrane protein signaling highlights current state-of-the-art techniques being used, and showcases the rising power of computational methods to complement traditional wet experiments in bringing the plentiful structural models to life.

The Perspective in this issue on HERG channels, from recent Cole Award recipient Gail Robertson and Joao Morais Cabral, outlines the current understanding of function in these essential cardiac ion channels in the context of recent structures (Robertson). Other papers exploit structural data to build compelling studies of the role of residues lining the channel of acid sensing channels (Pless), the voltage sensing domains of potassium channels (Bezanilla), and the activation of transient receptor potential channels (Islas). Classical electrophysiological measurements are used to study the question of calcium-dependent inactivation in single N-methyl D-Aspartate receptors (Popescu), and to make real-time measurements of protein dynamics from membrane surface potentials (Sandtner). Molecular dynamic simulations are presented for understanding magnesium ion binding sites in mu-opioid G protein-coupled receptors (Filizola), and the effect of DHHC20 palmitoyl transferase (Gomez) in mediating changes at the membrane.

Biophysical studies like those in this issue illustrate the vigor and invention in this research area. We sense, from the scope of papers that we received, that the once fanciful dream of integrating and mapping dynamic events at the membrane is closer than ever. Biophysicists working at the interface of computational, structural, and functional biology will play an essential role in developing such maps. We have been inspired by the breadth of work in this area, from control of chemical sensing in bacteria to signaling in nerve cells of the mammalian brain. We trust the readers of this special issue are similarly inspired to pursue cutting edge work in this ever evolving field.