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

James A. Stapleton, Timothy A. Whitehead, Vikas Nanda

Research output: Contribution to journalArticle

  • 10 Citations

Abstract

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 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.

LanguageEnglish (US)
Pages9632-9637
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number31
DOIs
StatePublished - Aug 4 2015

Profile

Membrane Proteins
Lipids
Protein Engineering
Cell Membrane
Escherichia coli
Amino Acids
Mutation
Membranes

Keywords

  • Membrane proteins
  • OmpA
  • Protein design
  • Statistical potential
  • β-barrel

ASJC Scopus subject areas

  • General

Cite this

Computational redesign of the lipid-facing surface of the outer membrane protein OmpA. / Stapleton, James A.; Whitehead, Timothy A.; Nanda, Vikas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 31, 04.08.2015, p. 9632-9637.

Research output: Contribution to journalArticle

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