Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes

• Main Author: Slavica Jonić
• Format: Article
• Language: English
• Published: Elsevier 2016-01-01
• Series: Computational and Structural Biotechnology Journal
• Subjects: Cryo-electron microscopy; Single particle analysis; Macromolecular complexes; Heterogeneity; Structure; Flexibility; Conformational changes; Dynamics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2001037016300551

Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.