Controlled Co-reconstitution of Multiple Membrane Proteins in Lipid Bilayer Nanodiscs Using DNA as a Scaffold

ACS Chem Biol. 2015 Nov 20;10(11):2448-54. doi: 10.1021/acschembio.5b00627. Epub 2015 Sep 21.

Abstract

Nanodiscs constitute a tool for the solubilization of membrane proteins in a lipid bilayer, thus offering a near-native membrane environment. Many membrane proteins interact with other membrane proteins; however, the co-reconstitution of multiple membrane proteins in a single nanodisc is a random process that is adversely affected by several factors, including protein aggregation. Here, we present an approach for the controlled co-reconstitution of multiple membrane proteins in a single nanodisc. The temporary attachment of designated oligonucleotides to individual membrane proteins enables the formation of stable, detergent-solubilized membrane protein complexes by base-pairing of complementary oligonucleotide sequences, thus facilitating the insertion of the membrane protein complex into nanodiscs with defined stoichiometry and composition. As a proof of principle, nanodiscs containing a heterodimeric and heterotrimeric membrane protein complex were reconstituted using a fluorescently labeled voltage-gated anion channel (VDAC) as a model system.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA / chemistry*
  • Fluorescent Dyes / chemistry
  • Ion Channels / chemistry
  • Lipid Bilayers / chemistry*
  • Membrane Proteins / chemistry*
  • Microscopy, Fluorescence
  • Models, Biological
  • Nanostructures / chemistry*
  • Nuclear Matrix / chemistry*

Substances

  • Fluorescent Dyes
  • Ion Channels
  • Lipid Bilayers
  • Membrane Proteins
  • DNA