De novo design of defined helical bundles in membrane environments

Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15324-9. doi: 10.1073/pnas.0403314101. Epub 2004 Oct 14.

Abstract

Control of structure and function in membrane proteins remains a formidable challenge. We report here a new design paradigm for the self-assembly of protein components in the context of nonpolar environments of biological membranes. An incrementally staged assembly process relying on the unique properties of fluorinated amino acids was used to drive transmembrane helix-helix interactions. In the first step, hydrophobic peptides partitioned into micellar lipids. Subsequent phase separation of simultaneously hydrophobic and lipophobic fluorinated helical surfaces fueled spontaneous self-assembly of higher order oligomers. The creation of these ordered transmembrane protein ensembles is supported by gel electrophoresis, circular dichroism spectroscopy, equilibrium analytical ultracentrifugation, and fluorescence resonance energy transfer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Ultracentrifugation

Substances

  • Membrane Proteins