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Title: Intermolecular correlations are necessary to explain diffuse scattering from protein crystals

Abstract

Conformational changes drive protein function, including catalysis, allostery, and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signal reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate amore » need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.« less

Authors:
 [1];  [2];  [3]
  1. Stanford Univ., CA (United States). Dept. of Biochemistry
  2. Stanford Univ., CA (United States). Dept. of Structural Biology; SLAC National Accelerator Lab., Menlo Park, CA (United States). Photon Ultrafast Laser Science and Engineering Inst. (PULSE)
  3. SLAC National Accelerator Lab., Menlo Park, CA (United States). Linac Coherent Light Source (LCLS) and Bioscience Division
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1417038
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
IUCrJ
Additional Journal Information:
Journal Volume: 5; Journal Issue: 2; Journal ID: ISSN 2052-2525
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; diffuse scattering; intermolecular correlations

Citation Formats

Peck, Ariana, Poitevin, Frederic, and Lane, Thomas Joseph. Intermolecular correlations are necessary to explain diffuse scattering from protein crystals. United States: N. p., 2018. Web. https://doi.org/10.1107/S2052252518001124.
Peck, Ariana, Poitevin, Frederic, & Lane, Thomas Joseph. Intermolecular correlations are necessary to explain diffuse scattering from protein crystals. United States. https://doi.org/10.1107/S2052252518001124
Peck, Ariana, Poitevin, Frederic, and Lane, Thomas Joseph. Wed . "Intermolecular correlations are necessary to explain diffuse scattering from protein crystals". United States. https://doi.org/10.1107/S2052252518001124. https://www.osti.gov/servlets/purl/1417038.
@article{osti_1417038,
title = {Intermolecular correlations are necessary to explain diffuse scattering from protein crystals},
author = {Peck, Ariana and Poitevin, Frederic and Lane, Thomas Joseph},
abstractNote = {Conformational changes drive protein function, including catalysis, allostery, and signaling. X-ray diffuse scattering from protein crystals has frequently been cited as a probe of these correlated motions, with significant potential to advance our understanding of biological dynamics. However, recent work challenged this prevailing view, suggesting instead that diffuse scattering primarily originates from rigid body motions and could therefore be applied to improve structure determination. To investigate the nature of the disorder giving rise to diffuse scattering, and thus the potential applications of this signal, a diverse repertoire of disorder models was assessed for its ability to reproduce the diffuse signal reconstructed from three protein crystals. This comparison revealed that multiple models of intramolecular conformational dynamics, including ensemble models inferred from the Bragg data, could not explain the signal. Models of rigid body or short-range liquid-like motions, in which dynamics are confined to the biological unit, showed modest agreement with the diffuse maps, but were unable to reproduce experimental features indicative of long-range correlations. Extending a model of liquid-like motions to include disorder across neighboring proteins in the crystal significantly improved agreement with all three systems and highlighted the contribution of intermolecular correlations to the observed signal. These findings anticipate a need to account for intermolecular disorder in order to advance the interpretation of diffuse scattering to either extract biological motions or aid structural inference.},
doi = {10.1107/S2052252518001124},
journal = {IUCrJ},
number = 2,
volume = 5,
place = {United States},
year = {2018},
month = {2}
}

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Cited by: 3 works
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