Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution, new validation tools, and implications for the future

Stephen K Burley; Helen M Berman; Wah Chiu; Wei Dai; Justin W Flatt; Brian P Hudson; Jason T Kaelber; Sagar D Khare; Arkadiusz W Kulczyk; Catherine L Lawson; Grigore D Pintilie; Andrej Sali; Brinda Vallat; John D Westbrook; Jasmine Y Young; Christine Zardecki

doi:10.1007/s12551-022-01013-w

Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution, new validation tools, and implications for the future

Biophys Rev. 2022 Dec 2;14(6):1281-1301. doi: 10.1007/s12551-022-01013-w. eCollection 2022 Dec.

Authors

Stephen K Burley^{1

2

3

4

5}, Helen M Berman^{1

2

5}, Wah Chiu^{6

7}, Wei Dai^{2

8}, Justin W Flatt^{1

2}, Brian P Hudson^{1

2}, Jason T Kaelber², Sagar D Khare^{2

3

5}, Arkadiusz W Kulczyk^{2

9}, Catherine L Lawson^{1

2}, Grigore D Pintilie⁶, Andrej Sali¹⁰, Brinda Vallat^{1

2

3}, John D Westbrook^{1

2

3}, Jasmine Y Young^{1

2}, Christine Zardecki^{1

2}

Affiliations

¹ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
² Institute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
³ Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 USA.
⁴ Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093 USA.
⁵ Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854 USA.
⁶ Department of Bioengineering, Stanford University, Stanford, CA USA.
⁷ Division of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA USA.
⁸ Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
⁹ Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08901 USA.
¹⁰ Research Collaboratory for Structural Bioinformatics Protein Data Bank, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA 94158 USA.

Abstract

As a discipline, structural biology has been transformed by the three-dimensional electron microscopy (3DEM) "Resolution Revolution" made possible by convergence of robust cryo-preservation of vitrified biological materials, sample handling systems, and measurement stages operating a liquid nitrogen temperature, improvements in electron optics that preserve phase information at the atomic level, direct electron detectors (DEDs), high-speed computing with graphics processing units, and rapid advances in data acquisition and processing software. 3DEM structure information (atomic coordinates and related metadata) are archived in the open-access Protein Data Bank (PDB), which currently holds more than 11,000 3DEM structures of proteins and nucleic acids, and their complexes with one another and small-molecule ligands (~ 6% of the archive). Underlying experimental data (3DEM density maps and related metadata) are stored in the Electron Microscopy Data Bank (EMDB), which currently holds more than 21,000 3DEM density maps. After describing the history of the PDB and the Worldwide Protein Data Bank (wwPDB) partnership, which jointly manages both the PDB and EMDB archives, this review examines the origins of the resolution revolution and analyzes its impact on structural biology viewed through the lens of PDB holdings. Six areas of focus exemplifying the impact of 3DEM across the biosciences are discussed in detail (icosahedral viruses, ribosomes, integral membrane proteins, SARS-CoV-2 spike proteins, cryogenic electron tomography, and integrative structure determination combining 3DEM with complementary biophysical measurement techniques), followed by a review of 3DEM structure validation by the wwPDB that underscores the importance of community engagement.

Keywords: Cryo-electron microscopy; Cryo-electron tomography; EMDB; Electron Microscopy Data Bank; Electron crystallography; Electron microscopy; Electron microscopy data resource; Icosahedral viruses; Integral membrane proteins; Integrative or hybrid methods; Micro-electron diffraction; PDB; PDB-Dev; Protein Data Bank; Q-score; Resolution Revolution; Ribosomes; SARS-CoV-2 spike proteins; Structure validation; Sub-tomogram averaging.

Publication types

Review

Abstract

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