Overview of electron crystallography of membrane proteins: crystallization and screening strategies using negative stain electron microscopy

Curr Protoc Protein Sci. 2013:Chapter 17:Unit17.15. doi: 10.1002/0471140864.ps1715s72.

Abstract

Electron cryomicroscopy, or cryoEM, is an emerging technique for studying the three-dimensional structures of proteins and large macromolecular machines. Electron crystallography is a branch of cryoEM in which structures of proteins can be studied at resolutions that rival those achieved by X-ray crystallography. Electron crystallography employs two-dimensional crystals of a membrane protein embedded within a lipid bilayer. The key to a successful electron crystallographic experiment is the crystallization, or reconstitution, of the protein of interest. This unit describes ways in which protein can be expressed, purified, and reconstituted into well-ordered two-dimensional crystals. A protocol is also provided for negative stain electron microscopy as a tool for screening crystallization trials. When large and well-ordered crystals are obtained, the structures of both protein and its surrounding membrane can be determined to atomic resolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy / methods*
  • Crystallography / methods*
  • Membrane Proteins / chemistry*
  • Molecular Conformation
  • Negative Staining / methods*

Substances

  • Membrane Proteins