Conformational Chaperones for Structural Studies of Membrane Proteins Using Antibody Phage Display with Nanodiscs

Structure. 2016 Feb 2;24(2):300-9. doi: 10.1016/j.str.2015.11.014. Epub 2015 Dec 31.


A major challenge in membrane biophysics is to define the mechanistic linkages between a protein's conformational transitions and its function. We describe a novel approach to stabilize transient functional states of membrane proteins in native-like lipid environments allowing for their structural and biochemical characterization. This is accomplished by combining the power of antibody Fab-based phage display selection with the benefits of embedding membrane protein targets in lipid-filled nanodiscs. In addition to providing a stabilizing lipid environment, nanodiscs afford significant technical advantages over detergent-based formats. This enables the production of a rich pool of high-performance Fab binders that can be used as crystallization chaperones, as fiducial markers for single-particle cryoelectron microscopy, and as probes of different conformational states. Moreover, nanodisc-generated Fabs can be used to identify detergents that best mimic native membrane environments for use in biophysical studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Surface Display Techniques / methods*
  • Detergents / chemistry
  • Immunoglobulin Fragments / chemistry*
  • Lipid Bilayers / chemistry
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Molecular Chaperones / chemistry*
  • Nanostructures / chemistry*
  • Peptide Library
  • Protein Conformation


  • Detergents
  • Immunoglobulin Fragments
  • Lipid Bilayers
  • Membrane Proteins
  • Molecular Chaperones
  • Peptide Library