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Lipid environment of membrane proteins in cryo-EM based structural analysis

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Abstract

Cryoelectron microscopy (cryo-EM) in association with a single particle analysis method (SPA) is now a promising tool to determine the structures of proteins and their macromolecular complexes. The development of direct electron detection cameras and image processing technologies has allowed the structures of many important proteins to be solved at near-atomic resolution or, in some cases, at atomic resolution, by overcoming difficulties in crystallization or low yield of protein production. In the case of membrane-integrated proteins, the proteins were traditionally solubilized and stabilized with various kind of detergents. However, the density of detergent micelles diminished the contrast of membrane proteins in cryo-EM studies and made it difficult to obtain high-resolution structures. To improve the resolution of membrane protein structures in cryo-EM studies, major improvements have been made both in sample preparation techniques and in hardware and software developments. The focus of our review is on improvements which have been made in the various techniques for sample preparation for cryo-EM studies, with a specific interest placed on techniques for mimicking the lipid environment of membrane proteins.

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Acknowledgments

This work was supported in part by Grant-in-Aid for Scientific Research on Priority Areas from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT).

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  1. AIST-UTokyo Advanced Operando-Measurement Technology Open Innovation Laboratory (OPERANDO-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Chiba, 277-8568, Japan

    Kazuhiro Mio

  2. Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan

    Kazuhiro Mio

  3. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, 305-8566, Japan

    Chikara Sato

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  1. Kazuhiro Mio
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This article is part of a Special Issue on ‘Biomolecules to Bio-nanomachines—Fumio Arisaka 70th Birthday’ edited by Damien Hall, Junichi Takagi and Haruki Nakamura

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Mio, K., Sato, C. Lipid environment of membrane proteins in cryo-EM based structural analysis. Biophys Rev 10, 307–316 (2018). https://doi.org/10.1007/s12551-017-0371-6

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  • DOI: https://doi.org/10.1007/s12551-017-0371-6

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