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Philos Trans R Soc Lond B Biol Sci. 2017 Aug 5;372(1726). pii: 20160213. doi: 10.1098/rstb.2016.0213.

Membrane-spanning α-helical barrels as tractable protein-design targets.

Author information

1
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
2
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK d.n.woolfson@bristol.ac.uk.
3
School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK.
4
BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, UK.

Abstract

The rational (de novo) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process. The α-helical coiled coil is a protein-structure element found in both globular and membrane proteins, where it cements a variety of helix-helix interactions and helical bundles. Our deep understanding of coiled coils has enabled a large number of successful de novo designs. For one class, the α-helical barrels-that is, symmetric bundles of five or more helices with central accessible channels-there are both water-soluble and membrane-spanning examples. Recent computational designs of water-soluble α-helical barrels with five to seven helices have advanced the design field considerably. Here we identify and classify analogous and more complicated membrane-spanning α-helical barrels from the Protein Data Bank. These provide tantalizing but tractable targets for protein engineering and de novo protein design.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'.

KEYWORDS:

coiled coil; de novo protein design; transmembrane proteins; α-helical barrel

PMID:
28630153
PMCID:
PMC5483516
DOI:
10.1098/rstb.2016.0213
[Indexed for MEDLINE]
Free PMC Article

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