Ab initio structure determination from prion nanocrystals at atomic resolution by MicroED

Sawaya, Michael R.; Rodriguez, Jose; Cascio, Duilio; Collazo, Michael J.; Shi, Dan; Reyes, Francis E.; Hattne, Johan; Gonen, Tamir; Eisenberg, David S.

doi:10.1073/pnas.1606287113

Title: Ab initio structure determination from prion nanocrystals at atomic resolution by MicroED

Journal Article · Mon Sep 19 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1606287113· OSTI ID:1425979

Sawaya, Michael R. ^[1]; Rodriguez, Jose ^[1]; Cascio, Duilio ^[1]; Collazo, Michael J. ^[1]; Shi, Dan ^[2]; Reyes, Francis E. ^[2];

^[2]; Gonen, Tamir ^[2]; Eisenberg, David S. ^[1]

Univ. of California, Los Angeles, CA (United States)
Howard Hughes Medical Inst., Ashburn, VA (United States)

Electrons, because of their strong interaction with matter, produce high-resolution diffraction patterns from tiny 3D crystals only a few hundred nanometers thick in a frozen-hydrated state. This discovery offers the prospect of facile structure determination of complex biological macromolecules, which cannot be coaxed to form crystals large enough for conventional crystallography or cannot easily be produced in sufficient quantities. Two potential obstacles stand in the way. The first is a phenomenon known as dynamical scattering, in which multiple scattering events scramble the recorded electron diffraction intensities so that they are no longer informative of the crystallized molecule. The second obstacle is the lack of a proven means of de novo phase determination, as is required if the molecule crystallized is insufficiently similar to one that has been previously determined.We showwith four structures of the amyloid core of the Sup35 prion protein that, if the diffraction resolution is high enough, sufficiently accurate phases can be obtained by direct methods with the cryo-EM method microelectron diffraction (MicroED), just as in X-ray diffraction. The success of these four experiments dispels the concern that dynamical scattering is an obstacle to ab initio phasing by MicroED and suggests that structures of novel macromolecules can also be determined by direct methods.

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Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: FC02-02ER63421

OSTI ID:: 1425979

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 40; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 66 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: Ab initio structure determination from prion nanocrystals at atomic resolution by MicroED

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