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Microcrystal electron diffraction
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<h2 id="development">Development</h2> <p class="note">See also: <a href="/facts/Electron_crystallography/RIMzhXpa">Electron crystallography § History</a></p> <p>Electron diffraction to solve crystal structures date back to the earliest days of electron diffraction. The first successful demonstration of MicroED was reported in 2013 by the <a href="/facts/Tamir_Gonen/HvWD5shE">Gonen</a> laboratory<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> for the structure of <a href="/facts/Lysozyme/VQqTSbFS">lysozyme</a>, a classic test protein in <a href="/facts/X-ray_crystallography/WtI0F5DN">X-ray crystallography</a>. </p> <h2 id="experimental-setup">Experimental setup</h2> <p>Detailed protocols for setting up the electron microscope and for data collections have been published.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> </p> <h3>Instrumentation</h3> <h4>Microscope</h4> <p>MicroED data is collected using <a href="/facts/Transmission_electron_cryomicroscopy/41cuVGW7">transmission electron (cryogenic) microscopy</a>. The microscope can be equipped with a selected area aperture but MicroED can also be done without a selected area aperture. While some structures have been reported without freezing, radiation damage is sometimes minimized and higher resolution obtained by using cryo cooling even for small molecules.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p> <h4>Detectors</h4> <p>A variety of detectors have been used to collected electron diffraction data in MicroED experiments. Detectors utilizing <a href="/facts/Charge-coupled_device/l6xffIcz">charge-coupled device (CCD)</a> and <a href="/facts/CMOS/7g2EwHGA">complementary metal–oxide–semiconductor (CMOS)</a> technology have been used. With CMOS detectors, individual electron counts can be interpreted.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> More recently, direct electron detectors have been successfully used in both linear and counting modes.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a><a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> In these examples electron counting allowed ab initio phasing and visualization of hydrogens in proteins. </p> <h3>Data collection</h3> <h4>Still diffraction</h4> <p>The initial proof of concept publication on MicroED used lysozyme crystals.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> Up to 90 degrees of data were collected from a single nano crystal, with discrete 1 degree steps between frames. Each diffraction pattern was collected with an ultra-low dose rate of ~0.01 e−/Å2/s. Data from 3 crystals was merged<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> to yield a 2.9Å resolution structure with good refinement statistics, enabling determination of the structure of a dose-sensitive protein from 3D microcrystals in cryogenic conditions. </p> <h4>Continuous rotation</h4> <p>MicroED uses continuous rotation during the data collection scheme.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> Here the crystal is slowly rotated in a single direction while diffraction is recorded on a fast camera as a movie. This led to several improvements in data quality and allowed data processing using standard X-ray crystallographic software.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Continuous rotation MicroED improves sampling of reciprocal space.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> </p> <h3>Data processing</h3> <p>Detailed protocols for MicroED data processing have been published.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> When MicroED data is collected using continuous stage rotation, standard crystallography software<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> can be used. </p> <h2 id="differences-between-microed-and-other-electron-diffraction-methods">Differences between MicroED and other electron diffraction methods</h2> <p>Other electron diffraction methods that have been developed and demonstrated to work include Automated Diffraction Tomography (ADT)<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> and Rotation Electron Diffraction (RED<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a>). These methods differ slightly from MicroED: In ADT discrete steps of <a href="/facts/Goniometer/T9PDB4yf">goniometer</a> tilt are used to cover reciprocal space in combination with beam precession to reduce dynamical diffraction effects.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> ADT uses hardware and software for precession and scanning transmission electron microscopy for crystal tracking.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> RED is done in TEM but the goniometer is tilted in discrete steps and beam tilting is used to fill in the gaps.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> Software is used to process ADT and RED data.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p> <h2 id="milestones">Milestones</h2> <h3>Method scope</h3> <p>MicroED has been used to determine the structures of large globular proteins,<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> small proteins,<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> peptides,<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> membrane proteins,<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> organic molecules,<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> and inorganic compounds.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> In many of these examples hydrogens and charged ions were observed.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a><a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p> <h3>Novel structures of α-synuclein of Parkinson's disease</h3> <p>The first structures solved by MicroED were published in late 2015.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> These structures were of peptide fragments that form the toxic core of <a href="/facts/Alpha-synuclein/rMau6thf">α-synculein</a>, the protein responsible for <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a> and lead to insight into the aggregation mechanism toxic aggregates. The structures were solved at 1.4 Å resolution. </p> <h3>Novel protein structure of R2lox</h3> <p>The first novel structure of a protein solved by MicroED was published in 2019.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> The protein is the metalloenzyme R2-like ligand-binding oxidase (R2lox) from Sulfolobus acidocaldarius. The structure was solved at 3.0 Å resolution by molecular replacement using a model of 35% sequence identity built from the closest homolog with a known structure. </p> <h2 id="further-reading">Further reading</h2> <ul><li><a href="https://www.thermofisher.com/us/en/home/electron-microscopy/life-sciences/microed.html">Background on MicroED from ThermoFisher Scientific, a major producer of transmission electron microscopes</a> <ul><li><a href="https://www.thermofisher.com/us/en/home/electron-microscopy/life-sciences/microed.html?playlistVideoId=6125661804001">Video interview about the development of MicroED and its applications</a></li></ul></li> <li><a href="https://www.janelia.org/archive/micro-electron-diffraction-microed">The Janelia Archives background on MicroED</a></li> <li><a href="https://cryoem.ucla.edu/microed">Background and publications on MicroED from the Gonen Laboratory</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Shi, Dan; Nannenga, Brent L; Iadanza, Matthew G; Gonen, Tamir (2013-11-19). "Three-dimensional electron crystallography of protein microcrystals". eLife. 2: e01345. doi:10.7554/elife.01345. ISSN 2050-084X. PMC 3831942. PMID 24252878. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Gonen, Tamir; Sliz, Piotr; Kistler, Joerg; Cheng, Yifan; Walz, Thomas (May 2004). "Aquaporin-0 membrane junctions reveal the structure of a closed water pore". Nature. 429 (6988): 193–197. doi:10.1038/nature02503. ISSN 1476-4687. <a href="https://www.nature.com/articles/nature02503" target="_blank">https://www.nature.com/articles/nature02503</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Walz, Thomas; Hirai, Teruhisa; Murata, Kazuyoshi; Heymann, J. Bernard; Mitsuoka, Kaoru; Fujiyoshi, Yoshinori; Smith, Barbara L.; Agre, Peter; Engel, Andreas (June 1997). "The three-dimensional structure of aquaporin-1". Nature. 387 (6633): 624–627. doi:10.1038/42512. ISSN 0028-0836. <a href="http://www.nature.com/articles/42512" target="_blank">http://www.nature.com/articles/42512</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Laschkarew, W. E.; Usyskin, I. D. (1933). "Die Bestimmung der Lage der Wasserstoffionen im NH4Cl-Kristallgitter durch Elektronenbeugung". Zeitschrift für Physik (in German). 85 (9–10): 618–630. doi:10.1007/BF01331003. ISSN 1434-6001. <a href="http://link.springer.com/10.1007/BF01331003" target="_blank">http://link.springer.com/10.1007/BF01331003</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Takayanagi, K.; Tanishiro, Y.; Takahashi, M.; Takahashi, S. (1985-05-01). "Structural analysis of Si(111)-7×7 by UHV-transmission electron diffraction and microscopy". Journal of Vacuum Science & Technology A: Vacuum, Surfaces, and Films. 3 (3): 1502–1506. doi:10.1116/1.573160. ISSN 0734-2101. <a href="https://pubs.aip.org/jva/article/3/3/1502/212496/Structural-analysis-of-Si-111-7-7-by-UHV" target="_blank">https://pubs.aip.org/jva/article/3/3/1502/212496/Structural-analysis-of-Si-111-7-7-by-UHV</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Vincent, R.; Midgley, P.A. (1994). "Double conical beam-rocking system for measurement of integrated electron diffraction intensities". Ultramicroscopy. 53 (3): 271–282. doi:10.1016/0304-3991(94)90039-6. <a href="https://linkinghub.elsevier.com/retrieve/pii/0304399194900396" target="_blank">https://linkinghub.elsevier.com/retrieve/pii/0304399194900396</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>VAINSHTEIN, B.K. (1964), "Experimental Electron Diffraction Structure Investigations", Structure Analysis by Electron Diffraction, Elsevier, pp. 295–390, retrieved 2024-05-01 <a href="https://dx.doi.org/10.1016/b978-0-08-010241-2.50010-9" target="_blank">https://dx.doi.org/10.1016/b978-0-08-010241-2.50010-9</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Dorset, D. L. (1995-08-31). Structural Electron Crystallography. Springer Science & Business Media. ISBN 978-0-306-45049-5. <a href="978-0-306-45049-5" target="_blank">978-0-306-45049-5</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Shi, Dan; Nannenga, Brent L; de la Cruz, M Jason; Liu, Jinyang; Sawtelle, Steven; Calero, Guillermo; Reyes, Francis E; Hattne, Johan; Gonen, Tamir (May 2016). "The collection of MicroED data for macromolecular crystallography". Nature Protocols. 11 (5): 895–904. doi:10.1038/nprot.2016.046. ISSN 1754-2189. PMC 5357465. PMID 27077331. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357465" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357465</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>de la Cruz, M Jason; Hattne, Johan; Shi, Dan; Seidler, Paul; Rodriguez, Jose; Reyes, Francis E; Sawaya, Michael R; Cascio, Duilio; Weiss, Simon C (2017). "Atomic-resolution structures from fragmented protein crystals with the cryoEM method MicroED". Nature Methods. 14 (4): 399–402. doi:10.1038/nmeth.4178. ISSN 1548-7091. PMC 5376236. PMID 28192420. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376236" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376236</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Hattne, Johan; Reyes, Francis E.; Nannenga, Brent L.; Shi, Dan; de la Cruz, M. Jason; Leslie, Andrew G. W.; Gonen, Tamir (2015-07-01). "MicroED data collection and processing". Acta Crystallographica Section A. 71 (4): 353–360. doi:10.1107/s2053273315010669. ISSN 2053-2733. PMC 4487423. PMID 26131894. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487423" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487423</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Zatsepin, Nadia A; Li, Chufeng; Colasurd, Paige; Nannenga, Brent L (October 2019). "The complementarity of serial femtosecond crystallography and MicroED for structure determination from microcrystals". Current Opinion in Structural Biology. 58: 286–293. doi:10.1016/j.sbi.2019.06.004. PMC 6778504. PMID 31345629. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778504" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778504</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Nannenga, Brent L.; Gonen, Tamir (May 2019). "The cryo-EM method microcrystal electron diffraction (MicroED)". Nature Methods. 16 (5): 369–379. doi:10.1038/s41592-019-0395-x. ISSN 1548-7091. PMC 6568260. PMID 31040436. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568260" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568260</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Shi, Dan; Nannenga, Brent L; Iadanza, Matthew G; Gonen, Tamir (2013-11-19). "Three-dimensional electron crystallography of protein microcrystals". eLife. 2: e01345. doi:10.7554/elife.01345. ISSN 2050-084X. PMC 3831942. PMID 24252878. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Shi, Dan; Nannenga, Brent L; de la Cruz, M Jason; Liu, Jinyang; Sawtelle, Steven; Calero, Guillermo; Reyes, Francis E; Hattne, Johan; Gonen, Tamir (2016-04-14). "The collection of MicroED data for macromolecular crystallography". Nature Protocols. 11 (5): 895–904. doi:10.1038/nprot.2016.046. ISSN 1754-2189. PMC 5357465. PMID 27077331. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357465" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357465</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Christensen, Jeppe; Horton, Peter N.; Bury, Charles S.; Dickerson, Joshua L.; Taberman, Helena; Garman, Elspeth F.; Coles, Simon J. (2019-07-01). "Radiation damage in small-molecule crystallography: fact not fiction". IUCrJ. 6 (4): 703–713. doi:10.1107/S2052252519006948. ISSN 2052-2525. PMC 6608633. PMID 31316814. <a href="https://scripts.iucr.org/cgi-bin/paper?S2052252519006948" target="_blank">https://scripts.iucr.org/cgi-bin/paper?S2052252519006948</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>See also https://www.gatan.com/ccd-vs-cmos and https://www.gatan.com/techniques/imaging. <a href="https://www.gatan.com/ccd-vs-cmos" target="_blank">https://www.gatan.com/ccd-vs-cmos</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Martynowycz, Michael W.; Clabbers, Max T. B.; Hattne, Johan; Gonen, Tamir (June 2022). "Ab initio phasing macromolecular structures using electron-counted MicroED data". Nature Methods. 19 (6): 724–729. doi:10.1038/s41592-022-01485-4. ISSN 1548-7091. PMC 9184278. PMID 35637302. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184278" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184278</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Clabbers, Max T.B.; Martynowycz, Michael W.; Hattne, Johan; Gonen, Tamir (2022). "Hydrogens and hydrogen-bond networks in macromolecular MicroED data". Journal of Structural Biology: X. 6: 100078. doi:10.1016/j.yjsbx.2022.100078. PMC 9731847. PMID 36507068. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731847" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731847</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Shi, Dan; Nannenga, Brent L; Iadanza, Matthew G; Gonen, Tamir (2013-11-19). "Three-dimensional electron crystallography of protein microcrystals". eLife. 2: e01345. doi:10.7554/elife.01345. ISSN 2050-084X. PMC 3831942. PMID 24252878. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>Shi, Dan; Nannenga, Brent L; Iadanza, Matthew G; Gonen, Tamir (2013-11-19). "Three-dimensional electron crystallography of protein microcrystals". eLife. 2: e01345. doi:10.7554/eLife.01345. ISSN 2050-084X. PMC 3831942. PMID 24252878. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831942</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (September 2014). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Hattne, Johan; Reyes, Francis E.; Nannenga, Brent L.; Shi, Dan; de la Cruz, M. Jason; Leslie, Andrew G. W.; Gonen, Tamir (2015-07-01). "MicroED data collection and processing". Acta Crystallographica Section A. 71 (4): 353–360. doi:10.1107/s2053273315010669. ISSN 2053-2733. PMC 4487423. PMID 26131894. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487423" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487423</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Nannenga, Brent L.; Gonen, Tamir (May 2019). "The cryo-EM method microcrystal electron diffraction (MicroED)". Nature Methods. 16 (5): 369–379. doi:10.1038/s41592-019-0395-x. ISSN 1548-7091. PMC 6568260. PMID 31040436. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568260" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568260</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>Mugnaioli, E.; Gorelik, T.; Kolb, U. (2009). ""Ab initio" structure solution from electron diffraction data obtained by a combination of automated diffraction tomography and precession technique". Ultramicroscopy. 109 (6): 758–765. doi:10.1016/j.ultramic.2009.01.011. ISSN 0304-3991. PMID 19269095. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>Wan, Wei; Sun, Junliang; Su, Jie; Hovmöller, Sven; Zou, Xiaodong (2013-11-15). "Three-dimensional rotation electron diffraction: softwareREDfor automated data collection and data processing". Journal of Applied Crystallography. 46 (6): 1863–1873. doi:10.1107/s0021889813027714. ISSN 0021-8898. PMC 3831301. PMID 24282334. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>Mugnaioli, E.; Gorelik, T.; Kolb, U. (2009). ""Ab initio" structure solution from electron diffraction data obtained by a combination of automated diffraction tomography and precession technique". Ultramicroscopy. 109 (6): 758–765. doi:10.1016/j.ultramic.2009.01.011. ISSN 0304-3991. PMID 19269095. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>Mugnaioli, E.; Gorelik, T.; Kolb, U. (2009). ""Ab initio" structure solution from electron diffraction data obtained by a combination of automated diffraction tomography and precession technique". Ultramicroscopy. 109 (6): 758–765. doi:10.1016/j.ultramic.2009.01.011. ISSN 0304-3991. PMID 19269095. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></p></li> <li id="fn:34"><p>Wan, Wei; Sun, Junliang; Su, Jie; Hovmöller, Sven; Zou, Xiaodong (2013-11-15). "Three-dimensional rotation electron diffraction: softwareREDfor automated data collection and data processing". Journal of Applied Crystallography. 46 (6): 1863–1873. doi:10.1107/s0021889813027714. ISSN 0021-8898. PMC 3831301. PMID 24282334. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></p></li> <li id="fn:35"><p>Wan, Wei; Sun, Junliang; Su, Jie; Hovmöller, Sven; Zou, Xiaodong (2013-11-15). "Three-dimensional rotation electron diffraction: softwareREDfor automated data collection and data processing". Journal of Applied Crystallography. 46 (6): 1863–1873. doi:10.1107/s0021889813027714. ISSN 0021-8898. PMC 3831301. PMID 24282334. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831301</a> <a href="#fnref:35" class="footnote-back-ref">↩</a></p></li> <li id="fn:36"><p>Nannenga, Brent L; Shi, Dan; Hattne, Johan; Reyes, Francis E; Gonen, Tamir (2014-10-10). "Structure of catalase determined by MicroED". eLife. 3: e03600. doi:10.7554/elife.03600. ISSN 2050-084X. PMC 4359365. PMID 25303172. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359365" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359365</a> <a href="#fnref:36" class="footnote-back-ref">↩</a></p></li> <li id="fn:37"><p>Nannenga, Brent L; Shi, Dan; Leslie, Andrew G W; Gonen, Tamir (2014-08-03). "High-resolution structure determination by continuous-rotation data collection in MicroED". Nature Methods. 11 (9): 927–930. doi:10.1038/nmeth.3043. ISSN 1548-7091. PMC 4149488. PMID 25086503. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149488</a> <a href="#fnref:37" class="footnote-back-ref">↩</a></p></li> <li id="fn:38"><p>Rodriguez, J.A.; Ivanova, M.; Sawaya, M.R.; Cascio, D.; Reyes, F.; Shi, D.; Johnson, L.; Guenther, E.; Sangwan, S. (2015-09-09). "MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56". doi:10.2210/pdb4znn/pdb. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:38" class="footnote-back-ref">↩</a></p></li> <li id="fn:39"><p>Liu, S.; Gonen, T. (2018-09-12). "MicroED structure of NaK ion channel reveals a process of Na+ partition into the selectivity filter". doi:10.2210/pdb6cpv/pdb. S2CID 240183721. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:39" class="footnote-back-ref">↩</a></p></li> <li id="fn:40"><p>Gallagher-Jones, Marcus; Glynn, Calina; Boyer, David R.; Martynowycz, Michael W.; Hernandez, Evelyn; Miao, Jennifer; Zee, Chih-Te; Novikova, Irina V.; Goldschmidt, Lukasz (2018-01-15). "Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp". Nature Structural & Molecular Biology. 25 (2): 131–134. doi:10.1038/s41594-017-0018-0. ISSN 1545-9993. PMC 6170007. PMID 29335561. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170007" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170007</a> <a href="#fnref:40" class="footnote-back-ref">↩</a></p></li> <li id="fn:41"><p>Jones, Christopher; Martynowycz, M; Hattne, Johan; Fulton, Tyler J.; Stoltz, Brian M.; Rodriguez, Jose A.; Nelson, Hosea; Gonen, Tamir (2018). "The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination" (PDF). ACS Central Science. 4 (11): 1587–1592. doi:10.26434/chemrxiv.7215332.v1. PMC 6276044. PMID 30555912. <a href="https://authors.library.caltech.edu/90583/2/acscentsci.8b00760.pdf" target="_blank">https://authors.library.caltech.edu/90583/2/acscentsci.8b00760.pdf</a> <a href="#fnref:41" class="footnote-back-ref">↩</a></p></li> <li id="fn:42"><p>Vergara, Sandra; Lukes, Dylan A.; Martynowycz, Michael W.; Santiago, Ulises; Plascencia-Villa, Germán; Weiss, Simon C.; de la Cruz, M. Jason; Black, David M.; Alvarez, Marcos M. (2017-10-31). "MicroED Structure of Au146(p-MBA)57 at Subatomic Resolution Reveals a Twinned FCC Cluster". The Journal of Physical Chemistry Letters. 8 (22): 5523–5530. doi:10.1021/acs.jpclett.7b02621. ISSN 1948-7185. PMC 5769702. PMID 29072840. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769702" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769702</a> <a href="#fnref:42" class="footnote-back-ref">↩</a></p></li> <li id="fn:43"><p>Rodriguez, J.A.; Ivanova, M.; Sawaya, M.R.; Cascio, D.; Reyes, F.; Shi, D.; Johnson, L.; Guenther, E.; Sangwan, S. (2015-09-09). "MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56". doi:10.2210/pdb4znn/pdb. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:43" class="footnote-back-ref">↩</a></p></li> <li id="fn:44"><p>Liu, S.; Gonen, T. (2018-09-12). "MicroED structure of NaK ion channel reveals a process of Na+ partition into the selectivity filter". doi:10.2210/pdb6cpv/pdb. S2CID 240183721. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:44" class="footnote-back-ref">↩</a></p></li> <li id="fn:45"><p>Rodriguez, J.A.; Ivanova, M.; Sawaya, M.R.; Cascio, D.; Reyes, F.; Shi, D.; Johnson, L.; Guenther, E.; Sangwan, S. (2015-09-09). "MicroED structure of the segment, GVVHGVTTVA, from the A53T familial mutant of Parkinson's disease protein, alpha-synuclein residues 47-56". doi:10.2210/pdb4znn/pdb. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:45" class="footnote-back-ref">↩</a></p></li> <li id="fn:46"><p>Xu, Hongyi; Lebrette, Hugo; Clabbers, Max T. B.; Zhao, Jingjing; Griese, Julia J.; Zou, Xiaodong; Högbom, Martin (7 August 2019). "Solving a new R2lox protein structure by microcrystal electron diffraction". Science Advances. 5 (8): eaax4621. doi:10.1126/sciadv.aax4621. PMC 6685719. PMID 31457106. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685719" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685719</a> <a href="#fnref:46" class="footnote-back-ref">↩</a></p></li> </ol>