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Computational redesign of the lipid-facing surface of the outer membrane protein OmpA.

ABSTRACT: Advances in computational design methods have made possible extensive engineering of soluble proteins, but designed ?-barrel membrane proteins await improvements in our understanding of the sequence determinants of folding and stability. A subset of the amino acid residues of membrane proteins interact with the cell membrane, and the design rules that govern this lipid-facing surface are poorly understood. We applied a residue-level depth potential for ?-barrel membrane proteins to the complete redesign of the lipid-facing surface of Escherichia coli OmpA. Initial designs failed to fold correctly, but reversion of a small number of mutations indicated by backcross experiments yielded designs with substitutions to up to 60% of the surface that did support folding and membrane insertion.

SUBMITTER: Stapleton JA

PROVIDER: S-EPMC4534290 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Computational redesign of the lipid-facing surface of the outer membrane protein OmpA.

Stapleton James A JA Whitehead Timothy A TA Nanda Vikas V

Proceedings of the National Academy of Sciences of the United States of America 20150721 31

Advances in computational design methods have made possible extensive engineering of soluble proteins, but designed β-barrel membrane proteins await improvements in our understanding of the sequence determinants of folding and stability. A subset of the amino acid residues of membrane proteins interact with the cell membrane, and the design rules that govern this lipid-facing surface are poorly understood. We applied a residue-level depth potential for β-barrel membrane proteins to the complete ...[more]

PMID: 26199411

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