Format

Send to

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

Design of self-assembling transmembrane helical bundles to elucidate principles required for membrane protein folding and ion transport.

Author information

1
Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA william.degrado@ucsf.edu.
2
Department of Computer Science, Dartmouth College, Hanover, NH 03755, USA.
3
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA.
4
Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
5
Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA nate.joh@amgen.com.

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

PMID:
28630154
PMCID:
PMC5483517
DOI:
10.1098/rstb.2016.0214
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center