Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination
Abstract
In the companion paper by Ufimtsev and Levitt [Ufimtsev IS, Levitt M (2019)Proc Natl Acad Sci USA, 10.1073/pnas.1821512116], we presented a method for unsupervised solution of protein crystal structures and demonstrated its utility by solving several test cases of known structure in the 2.9- to 3.45-Å resolution range. Here we apply this method to solve the crystal structure of a 966-amino acid construct of human lethal giant larvae protein (Lgl2) that resisted years of structure determination efforts, at 3.2-Å resolution. The structure was determined starting with a molecular replacement (MR) model identified by unsupervised refinement of a pool of 50 candidate MR models. This initial model had 2.8-Å RMSD from the solution. The solved structure was validated by comparison with a model subsequently derived from an alternative crystal form diffracting to higher resolution. This model could phase an anomalous difference Fourier map from an Hg derivative, and a single-wavelength anomalous dispersion phased density map made from these sites aligned with the refined structure.
- Authors:
-
- Stanford Univ. School of Medicine, Stanford, CA (United States)
- Publication Date:
- Research Org.:
- SLAC National Accelerator Lab., Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1532382
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 116; Journal Issue: 22; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Ufimtsev, Ivan S., Almagor, Lior, Weis, William I., and Levitt, Michael. Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination. United States: N. p., 2019.
Web. doi:10.1073/pnas.1821513116.
Ufimtsev, Ivan S., Almagor, Lior, Weis, William I., & Levitt, Michael. Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination. United States. https://doi.org/10.1073/pnas.1821513116
Ufimtsev, Ivan S., Almagor, Lior, Weis, William I., and Levitt, Michael. Tue .
"Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination". United States. https://doi.org/10.1073/pnas.1821513116. https://www.osti.gov/servlets/purl/1532382.
@article{osti_1532382,
title = {Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination},
author = {Ufimtsev, Ivan S. and Almagor, Lior and Weis, William I. and Levitt, Michael},
abstractNote = {In the companion paper by Ufimtsev and Levitt [Ufimtsev IS, Levitt M (2019)Proc Natl Acad Sci USA, 10.1073/pnas.1821512116], we presented a method for unsupervised solution of protein crystal structures and demonstrated its utility by solving several test cases of known structure in the 2.9- to 3.45-Å resolution range. Here we apply this method to solve the crystal structure of a 966-amino acid construct of human lethal giant larvae protein (Lgl2) that resisted years of structure determination efforts, at 3.2-Å resolution. The structure was determined starting with a molecular replacement (MR) model identified by unsupervised refinement of a pool of 50 candidate MR models. This initial model had 2.8-Å RMSD from the solution. The solved structure was validated by comparison with a model subsequently derived from an alternative crystal form diffracting to higher resolution. This model could phase an anomalous difference Fourier map from an Hg derivative, and a single-wavelength anomalous dispersion phased density map made from these sites aligned with the refined structure.},
doi = {10.1073/pnas.1821513116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 22,
volume = 116,
place = {United States},
year = {2019},
month = {5}
}
Web of Science
Figures / Tables:

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