Design of Self-Assembling Transmembrane Helical Bundles to Elucidate Principles Required for Membrane Protein Folding and Ion Transport

Philos Trans R Soc Lond B Biol Sci. 2017 Aug 5;372(1726):20160214. doi: 10.1098/rstb.2016.0214.

Abstract

Ion transporters and channels are able to identify and act on specific substrates among myriads of ions and molecules critical to cellular processes, such as homeostasis, cell signalling, nutrient influx and drug efflux. Recently, we designed Rocker, a minimalist model for Zn2+/H+ co-transport. The success of this effort suggests that de novo membrane protein design has now come of age so as to serve a key approach towards probing the determinants of membrane protein folding, assembly and function. Here, we review general principles that can be used to design membrane proteins, with particular reference to helical assemblies with transport function. We also provide new functional and NMR data that probe the dynamic mechanism of conduction through Rocker.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'.

Keywords: computational design; membrane protein folding; metallotransporter.

Publication types

  • Review

MeSH terms

  • Carrier Proteins / chemistry*
  • Ion Transport
  • Membrane Proteins / chemistry*
  • Molecular Dynamics Simulation
  • Protein Engineering*
  • Protein Structure, Secondary

Substances

  • Carrier Proteins
  • Membrane Proteins
  • zinc-binding protein