Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination

doi:10.1073/pnas.1821513116

Title: 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:

^[1]; Almagor, Lior ^[1]; Weis, William I. ^[1];

^[1]

Stanford Univ. School of Medicine, Stanford, CA (United States)

Publication Date:: 2019-05-14

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.

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                    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.  doi:10.1073/pnas.1821513116.

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                    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.  doi:10.1073/pnas.1821513116.  https://www.osti.gov/servlets/purl/1532382.

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@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}

}

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DOI: 10.1073/pnas.1821513116

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Works referenced in this record:

Coot model-building tools for molecular graphics
journal, November 2004

Emsley, Paul; Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
DOI: 10.1107/S0907444904019158

PHENIX: a comprehensive Python-based system for macromolecular structure solution
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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

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Title: Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination

Abstract

Citation Formats

Coot model-building tools for molecular graphics journal, November 2004

PHENIX: a comprehensive Python-based system for macromolecular structure solution journal, January 2010

Coot model-building tools for molecular graphics
journal, November 2004

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010