Three-dimensional transmission electron microscopy (3DEM) is emerging as a powerful method for determining the three-dimensional structures of large biological assemblies in solution and in the cell, enabling elucidation of complex biological interactions that are integral to understanding the inner workings of cellular machinery, and yielding novel insights into fundamental biological processes. Hundreds of 3DEM experiments are now reported in the literature each year and more than 1,300 structures are available in public archives through EMDataBank (EMDataBank.org). The major goal of this project is to establish methods to assess the reliability of these structures and to create uniform standards for data exchange, in order to bridge the current substantial gap between 3DEM and established structure determination methods (X-ray crystallography and NMR) in the ability to evaluate and interpret the experimental results. EMDataBank will take a leadership role in facilitating the processes necessary to assess, establish, and disseminate validation methods and data standards. The approach will leverage the expertise and experience of the EMDataBank team in validation, standards, and 3DEM methods development. Validation methods for both 3DEM maps and map-derived models will be established using our own test data sets and software packages as well as those contributed by other electron microscopists. Our results will be made publicly available for comment and review on the EMDataBank website. The PDB exchange dictionary will be extended to support 3DEM community-reviewed validation procedures. Map and map-derived model validation procedures developed through this project will be integrated into the deposition and annotation pipeline of the Protein Data Bank. The work is expected to have a strong transformative impact on both the 3DEM and the wider bioscience communities, enabling independent assessment and interpretation of 3DEM experimental results by both expert and non-expert scientists, and leading to higher reliability and improved consistency of 3DEM structure data.

Public Health Relevance

Three-dimensional transmission electron microscopy (3DEM) is an emerging powerful method for elucidating complex biological interactions that are integral to understanding the inner workings of cellular machinery, and yielding novel insights into fundamental biological processes. The EMDataBank project team will work to establish methods to assess the quality and accuracy of structures determined using 3DEM and to create uniform standards for data exchange, improving the reliability and consistency of data produced by this method.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079429-07
Application #
8663286
Study Section
Special Emphasis Panel (ZRG1-BCMB-B (02))
Program Officer
Flicker, Paula F
Project Start
2007-08-15
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
7
Fiscal Year
2014
Total Cost
$895,202
Indirect Cost
$117,847
Name
Baylor College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Berman, Helen M; Kleywegt, Gerard J; Nakamura, Haruki et al. (2014) The Protein Data Bank archive as an open data resource. J Comput Aided Mol Des 28:1009-14
Serysheva, Irina I (2014) Toward a high-resolution structure of IP?R channel. Cell Calcium 56:125-32
Wang, Zhao; Hryc, Corey F; Bammes, Benjamin et al. (2014) An atomic model of brome mosaic virus using direct electron detection and real-space optimization. Nat Commun 5:4808
Patwardhan, Ardan; Ashton, Alun; Brandt, Robert et al. (2014) A 3D cellular context for the macromolecular world. Nat Struct Mol Biol 21:841-5
Gutmanas, Aleksandras; Alhroub, Younes; Battle, Gary M et al. (2014) PDBe: Protein Data Bank in Europe. Nucleic Acids Res 42:D285-91
Gipson, Preeti; Baker, Matthew L; Raytcheva, Desislava et al. (2014) Protruding knob-like proteins violate local symmetries in an icosahedral marine virus. Nat Commun 5:4278
Berman, Helen M; Kleywegt, Gerard J; Nakamura, Haruki et al. (2013) How community has shaped the Protein Data Bank. Structure 21:1485-91
Gutmanas, Aleksandras; Oldfield, Thomas J; Patwardhan, Ardan et al. (2013) The role of structural bioinformatics resources in the era of integrative structural biology. Acta Crystallogr D Biol Crystallogr 69:710-21
Zhang, Qinfen; Dai, Xinghong; Cong, Yao et al. (2013) Cryo-EM structure of a molluscan hemocyanin suggests its allosteric mechanism. Structure 21:604-13
Lagerstedt, Ingvar; Moore, William J; Patwardhan, Ardan et al. (2013) Web-based visualisation and analysis of 3D electron-microscopy data from EMDB and PDB. J Struct Biol 184:173-81

Showing the most recent 10 out of 32 publications