4D Liquid-phase Electron Microscopy of Ferritin by Brownian Single Particle Analysis

Protein function and activity are a consequence of its three-dimensional structure. Single particle analysis of cryogenic electron micrographs has radically changed structural biology allowing atomic reconstruction of almost any type of proteins. While such an approach provides snapshots of three-di...

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Bibliographic Details
Published in:arXiv.org 2019-07
Main Authors: Marchello, Gabriele, De Pace, Cesare, Wilkinson, Neil, Ruiz-Perez, Lorena, Battaglia, Giuseppe
Format: Article
Language:English
Subjects:
Algorithms
Biology
Brownian motion
Electron micrographs
Electron microscopy
Ferritin
Heat treating
Liquid phases
Microscopy
Proteins
Three dimensional analysis
Variation
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Summary:Protein function and activity are a consequence of its three-dimensional structure. Single particle analysis of cryogenic electron micrographs has radically changed structural biology allowing atomic reconstruction of almost any type of proteins. While such an approach provides snapshots of three-dimensional structural information that can be correlated with function, the new frontier of protein structural biology is in the fourth dimension, time. Here we propose the use of liquid phase electron microscopy to expand structural biology into dynamic studies. We apply here single particle analysis algorithm to images of proteins in Brownian motion through time; thus, Brownian single particle analysis (BSPA). BSPA enables to reduce the acquisition time from hours, in cryo-EM, to seconds and achieve information on conformational changes, hydration dynamics, and effects of thermal fluctuations. Yielding all these previously neglected aspects, BSPA may lead to the verge of a new field: dynamic structural biology.
ISSN:2331-8422