Self-assembly of single integral membrane proteins into soluble nanoscale phospholipid bilayers.
One of the biggest challenges in pharmaceutical research is obtaining integral membrane proteins in a functional, solubilized, and monodisperse state that provides a native-like environment that maintains the spectrum of in vivo activities. Many of these integral membrane proteins are receptors, enzymes, or other macromolecular assemblies that are important drug targets. An example is the general class of proteins composed of seven-transmembrane segments (7-TM) as exemplified by the G-protein-coupled receptors. In this article, we describe a simple system for self-assembling bacteriorhodopsin, as a model protein containing 7-TM helices, with phospholipids to form a nanometer-scale soluble bilayer structure encircled by a 200 amino acid scaffold protein. The result is the single molecule incorporation of an integral membrane protein target into a soluble and monodisperse structure that allows the structural and functional tools of solution biochemistry to be applied.
Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA.
Timothy H
TH
Bayburt
Stephen G
SG
Sligar
D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry*; D019617:Halobacterium salinarum / Q000737:chemistry; D008051:Lipid Bilayers / Q000138:chemical synthesis / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D043942:Nanotubes / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011485:Protein Binding
D008051:Lipid Bilayers; D008565:Membrane Proteins; D010743:Phospholipids; D001436:Bacteriorhodopsins