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Atomic resolution cryo-EM structure of β-galactosidase

TitleAtomic resolution cryo-EM structure of β-galactosidase
Publication TypeJournal Article
Year of Publication2018
AuthorsBartesaghi, A, Aguerrebere C, Falconieri V, Banerjee S, Earl LA, Zhu X, Grigorieff N, Milne JLS, Sapiro G, Wu X, Subramaniam S
Refereed DesignationRefereed
JournalStructure
Volume26
Pagination1-9
Date Published5/2018
ISSN09692126
Abstract

The advent of direct electron detectors has enabled the routine use of single-particle cryo-electron microscopy (EM) approaches to determine structures of a variety of protein complexes at near-atomic resolution. Here, we report the development of methods to account for local variations in defocus and beam-induced drift, and the implementation of a data-driven dose compensation scheme that significantly improves the extraction of high-resolution information recorded during exposure of the specimen to the electron beam. These advances enable determination of a cryo-EM density map for β-galactosidase bound to the inhibitor phenylethyl β-D-thiogalactopyranoside where the ordered regions are resolved at a level of detail seen in X-ray maps at ∼ 1.5 Å resolution. Using this density map in conjunction with constrained molecular dynamics simulations provides a measure of the local flexibility of the non-covalently bound inhibitor and offers further opportunities for structure-guided inhibitor design.

URLhttps://www.cell.com/structure/fulltext/S0969-2126(18)30129-1
DOI10.1016/j.str.2018.04.004
Short TitleStructure
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