Crossref journal-article
eLife Sciences Publications, Ltd
eLife (4374)
Abstract

Recent developments in detector hardware and image-processing software have revolutionized single particle cryo-electron microscopy (cryoEM) and led to a wave of near-atomic resolution (typically ∼3.3 Å) reconstructions. Reaching resolutions higher than 3 Å is a prerequisite for structure-based drug design and for cryoEM to become widely interesting to pharmaceutical industries. We report here the structure of the 700 kDa Thermoplasma acidophilum 20S proteasome (T20S), determined at 2.8 Å resolution by single-particle cryoEM. The quality of the reconstruction enables identifying the rotameric conformation adopted by some amino-acid side chains (rotamers) and resolving ordered water molecules, in agreement with the expectations for crystal structures at similar resolutions. The results described in this manuscript demonstrate that single particle cryoEM is capable of competing with X-ray crystallography for determination of protein structures of suitable quality for rational drug design.

Bibliography

Campbell, M. G., Veesler, D., Cheng, A., Potter, C. S., & Carragher, B. (2015). 2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy. ELife, 4. CLOCKSS.

Authors 5
  1. Melody G Campbell (first)
  2. David Veesler (additional)
  3. Anchi Cheng (additional)
  4. Clinton S Potter (additional)
  5. Bridget Carragher (additional)
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Dates
Type When
Created 10 years, 5 months ago (March 11, 2015, 8:33 a.m.)
Deposited 1 year, 10 months ago (Oct. 11, 2023, 8:47 p.m.)
Indexed 3 weeks, 4 days ago (July 30, 2025, 1:07 p.m.)
Issued 10 years, 5 months ago (March 11, 2015)
Published 10 years, 5 months ago (March 11, 2015)
Published Online 10 years, 5 months ago (March 11, 2015)
Funders 4
  1. National Institute of General Medical Sciences (NIGMS) 10.13039/100000057 National Institute of General Medical Sciences

    Region: Americas

    gov (National government)

    Labels2
    1. U.S. National Institute of General Medical Sciences
    2. NIGMS
    Awards1
    1. GM103310
  2. American Heart Association (AHA) 10.13039/100000968 American Heart Association

    Region: Americas

    gov (Associations and societies (private and public))

    Labels5
    1. American Heart Association, Inc.
    2. AMERICAN HEART ASSOC.
    3. American Heart Assn
    4. Association for the Prevention and Relief of Heart Disease
    5. AHA
    Awards1
    1. 14PRE18870036
  3. European Commission Directorate-General for Research and Innovation 10.13039/100004431 Directorate-General for Research and Innovation

    Region: Europe

    pri (International organizations)

    Labels1
    1. EC DG Research
    Awards1
    1. Marie Curie IOF fellowship (273427)
  4. National Institutes of Health (NIH) 10.13039/100000002 National Institutes of Health

    Region: Americas

    gov (National government)

    Labels3
    1. Institutos Nacionales de la Salud
    2. US National Institutes of Health
    3. NIH
    Awards1
    1. GM103310

@article{Campbell_2015, title={2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy}, volume={4}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.06380}, DOI={10.7554/elife.06380}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Campbell, Melody G and Veesler, David and Cheng, Anchi and Potter, Clinton S and Carragher, Bridget}, year={2015}, month=mar }