De novo design of transmembrane β barrels-Reference-Cited by-同舟云学术

De novo design of transmembrane β barrels

Published:2021-02-19 Issue:6531 Volume:371 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Vorobieva Anastassia A.¹²^ORCID,White Paul³^ORCID,Liang Binyong⁴^ORCID,Horne Jim E.³^ORCID,Bera Asim K.¹⁵,Chow Cameron M.¹⁵^ORCID,Gerben Stacey¹^ORCID,Marx Sinduja⁶^ORCID,Kang Alex¹⁵^ORCID,Stiving Alyssa Q.⁷,Harvey Sophie R.⁷^ORCID,Marx Dagan C.⁸^ORCID,Khan G. Nasir³^ORCID,Fleming Karen G.⁸^ORCID,Wysocki Vicki H.⁷^ORCID,Brockwell David J.³^ORCID,Tamm Lukas K.⁴^ORCID,Radford Sheena E.³^ORCID,Baker David¹²⁵^ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

2. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

3. Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, USA.

4. Department of Molecular Physiology and Biological Physics and Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, VA 22903, USA.

5. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

6. Department of Molecular Engineering and Sciences, University of Washington, Seattle, WA 98195, USA.

7. Department of Chemistry and Biochemistry, Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, USA.

8. TC Jenkins Department of Biophysics Johns Hopkins University, Baltimore, MD 21218, USA.

Abstract

Building a barrel Computational design offers the possibility of making proteins with customized structures and functions. The range of accessible protein scaffolds has expanded with the design of increasingly complex cytoplasmic proteins and, recently, helical membrane proteins. Vorobieva et al. describe the successful computational design of eight-stranded transmembrane β-barrel proteins (TMBs). Using an iterative approach, they show the importance of negative design to prevent off-target structures and gain insight into the sequence determinants of TMB folding. Twenty-three designs satisfied biochemical screens for a TMB structure, and two structures were experimentally validated by nuclear magnetic resonance spectroscopy or x-ray crystallography. This is a step toward the custom design of pores for applications such as single-molecule sequencing. Science , this issue p. eabc8182

Funder

National Institutes of Health

U.S. Department of Energy

Nordstrom Barrier Institute for Protein Design Directors Fund

Eric and Wendy Schmidt by recommendation of the the Schmidt Futures program

Howard Hughes Medical Institute

Air Force Office of Scientific Research

Open Philanthropy Project

Wellcome Trust Centre for Mitochondrial Research

Fulbright Belgium

Medical Research Council

Biotechnology and Biological Sciences Research Council