Vorobieva, AA, White, P orcid.org/0000-0001-7536-4552, Liang, B et al. (16 more authors) (2021) De novo design of transmembrane β-barrels. Science, 371 (6531). eabc8182. ISSN 0036-8075
Abstract
Transmembrane b-barrel proteins (TMBs) are of great interest for single-molecule analytical technologies because they can spontaneously fold and insert into membranes and form stable pores, but the range of pore properties that can be achieved by repurposing natural TMBs is limited. We leverage the power of de novo computational design coupled with a “hypothesis, design, and test” approach to determine TMB design principles, notably, the importance of negative design to slow b-sheet assembly. We design new eight-stranded TMBs, with no homology to known TMBs, that insert and fold reversibly into synthetic lipid membranes and have nuclear magnetic resonance and x-ray crystal structures very similar to the computational models. These advances should enable the custom design of pores for a wide range of applications.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2020 The Authors. This is an author-accepted version of a paper published in Science. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Structural Molecular Biology (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/P018491/1 Wellcome Trust 094232/Z/10/Z Wellcome Trust 094232/Z/10/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Feb 2021 14:10 |
Last Modified: | 26 Feb 2021 14:10 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Identification Number: | 10.1126/science.abc8182 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171520 |