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

Niitsu, A., Heal, J. W., Fauland, K., Thomson, A. R. , Woolfson, D. N. and Thomson, A. (2017) Membrane-spanning α-helical barrels as tractable protein-design targets. Philosophical Transactions of the Royal Society B: Biological Sciences, 372(1726), 20160213. (doi:10.1098/rstb.2016.0213) (PMID:28630153)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Dr Drew
Authors: Niitsu, A., Heal, J. W., Fauland, K., Thomson, A. R., Woolfson, D. N., and Thomson, A.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher:The Royal Society
ISSN:0962-8436
ISSN (Online):1471-2970
Published Online:19 June 2017

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