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Title: Accurate model annotation of a near-atomic resolution cryo-EM map

Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional uncertainty. Here, we introduce a computational procedure to derive an atomic model from a cryo- EM map with annotated metadata. The accuracy of such a model is validated by a faithful replication of the experimental cryo-EM map computed using the coordinates and associated metadata. The functional interpretation of any structural features in the model and its utilization for future studies can be made in the context of its measure of uncertainty. We applied this protocol to the 3.3-Å map of the mature P22 bacteriophage capsid, a large and complex macromolecular assembly. With this protocol, we identify and annotate previously undescribed molecular interactions between capsid subunits that are crucial to maintain stability in the absence of cementing proteins or cross-linking, as occur in other bacteriophages.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [2] ;  [4] ;  [5] ;  [3] ;  [4] ;  [6] ;  [6]
  1. Baylor College of Medicine, Houston, TX (United States). Graduate Program in Structural and Computational Biology and Molecular Biophysics
  2. Baylor College of Medicine, Houston, TX (United States). National Center for Macromolecular Imaging, Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
  4. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Biology
  5. Purdue Univ., West Lafayette, IN (United States). Dept. of Biological Sciences
  6. Baylor College of Medicine, Houston, TX (United States). Graduate Program in Structural and Computational Biology and Molecular Biophysics; Baylor College of Medicine, Houston, TX (United States). National Center for Macromolecular Imaging, Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
Publication Date:
Grant/Contract Number:
AC02-05CH11231; P01GM063210; P41GM103832; R01GM079429; PN2EY016525; T15LM007093
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 12; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH); Robert Welch Foundation
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; cryo-EM; P22; model; structure; annotation
OSTI Identifier:
1379782

Hryc, Corey F., Chen, Dong-Hua, Afonine, Pavel V., Jakana, Joanita, Wang, Zhao, Haase-Pettingell, Cameron, Jiang, Wen, Adams, Paul D., King, Jonathan A., Schmid, Michael F., and Chiu, Wah. Accurate model annotation of a near-atomic resolution cryo-EM map. United States: N. p., Web. doi:10.1073/pnas.1621152114.
Hryc, Corey F., Chen, Dong-Hua, Afonine, Pavel V., Jakana, Joanita, Wang, Zhao, Haase-Pettingell, Cameron, Jiang, Wen, Adams, Paul D., King, Jonathan A., Schmid, Michael F., & Chiu, Wah. Accurate model annotation of a near-atomic resolution cryo-EM map. United States. doi:10.1073/pnas.1621152114.
Hryc, Corey F., Chen, Dong-Hua, Afonine, Pavel V., Jakana, Joanita, Wang, Zhao, Haase-Pettingell, Cameron, Jiang, Wen, Adams, Paul D., King, Jonathan A., Schmid, Michael F., and Chiu, Wah. 2017. "Accurate model annotation of a near-atomic resolution cryo-EM map". United States. doi:10.1073/pnas.1621152114. https://www.osti.gov/servlets/purl/1379782.
@article{osti_1379782,
title = {Accurate model annotation of a near-atomic resolution cryo-EM map},
author = {Hryc, Corey F. and Chen, Dong-Hua and Afonine, Pavel V. and Jakana, Joanita and Wang, Zhao and Haase-Pettingell, Cameron and Jiang, Wen and Adams, Paul D. and King, Jonathan A. and Schmid, Michael F. and Chiu, Wah},
abstractNote = {Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atoms nor their positional uncertainty. Here, we introduce a computational procedure to derive an atomic model from a cryo- EM map with annotated metadata. The accuracy of such a model is validated by a faithful replication of the experimental cryo-EM map computed using the coordinates and associated metadata. The functional interpretation of any structural features in the model and its utilization for future studies can be made in the context of its measure of uncertainty. We applied this protocol to the 3.3-Å map of the mature P22 bacteriophage capsid, a large and complex macromolecular assembly. With this protocol, we identify and annotate previously undescribed molecular interactions between capsid subunits that are crucial to maintain stability in the absence of cementing proteins or cross-linking, as occur in other bacteriophages.},
doi = {10.1073/pnas.1621152114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 12,
volume = 114,
place = {United States},
year = {2017},
month = {3}
}

Works referenced in this record:

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925