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Title: Direct Observation of Insulin Association Dynamics with Time-Resolved X-ray Scattering

Abstract

Biological functions frequently require protein-protein interactions that involve secondary and tertiary structural perturbation. Here we study protein-protein dissociation and reassociation dynamics in insulin, a model system for protein oligomerization. Insulin dimer dissociation into monomers was induced by a nanosecond temperature-jump (T-jump) of ~8 °C in aqueous solution, and the resulting protein and solvent dynamics were tracked by time-resolved X-ray solution scattering (TRXSS) on time scales of 10 ns to 100 ms. The protein scattering signals revealed the formation of five distinguishable transient species during the association process that deviate from simple two state kinetics. Our results show that the combination of T-jump pump coupled to TRXSS probe allows for direct tracking of structural dynamics in nonphotoactive proteins.

Authors:
 [1];  [1];  [1];  [1];  [2]; ORCiD logo [3]
  1. Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
  2. Center for Advanced Radiation Sources, The University of Chicago, Chicago, Illinois 60637, United States
  3. Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States; Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, Illinois 60439, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1406920
DOE Contract Number:
AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Physical Chemistry Letters; Journal Volume: 8; Journal Issue: 18
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Rimmerman, Dolev, Leshchev, Denis, Hsu, Darren J., Hong, Jiyun, Kosheleva, Irina, and Chen, Lin X.. Direct Observation of Insulin Association Dynamics with Time-Resolved X-ray Scattering. United States: N. p., 2017. Web. doi:10.1021/acs.jpclett.7b01720.
Rimmerman, Dolev, Leshchev, Denis, Hsu, Darren J., Hong, Jiyun, Kosheleva, Irina, & Chen, Lin X.. Direct Observation of Insulin Association Dynamics with Time-Resolved X-ray Scattering. United States. doi:10.1021/acs.jpclett.7b01720.
Rimmerman, Dolev, Leshchev, Denis, Hsu, Darren J., Hong, Jiyun, Kosheleva, Irina, and Chen, Lin X.. 2017. "Direct Observation of Insulin Association Dynamics with Time-Resolved X-ray Scattering". United States. doi:10.1021/acs.jpclett.7b01720.
@article{osti_1406920,
title = {Direct Observation of Insulin Association Dynamics with Time-Resolved X-ray Scattering},
author = {Rimmerman, Dolev and Leshchev, Denis and Hsu, Darren J. and Hong, Jiyun and Kosheleva, Irina and Chen, Lin X.},
abstractNote = {Biological functions frequently require protein-protein interactions that involve secondary and tertiary structural perturbation. Here we study protein-protein dissociation and reassociation dynamics in insulin, a model system for protein oligomerization. Insulin dimer dissociation into monomers was induced by a nanosecond temperature-jump (T-jump) of ~8 °C in aqueous solution, and the resulting protein and solvent dynamics were tracked by time-resolved X-ray solution scattering (TRXSS) on time scales of 10 ns to 100 ms. The protein scattering signals revealed the formation of five distinguishable transient species during the association process that deviate from simple two state kinetics. Our results show that the combination of T-jump pump coupled to TRXSS probe allows for direct tracking of structural dynamics in nonphotoactive proteins.},
doi = {10.1021/acs.jpclett.7b01720},
journal = {Journal of Physical Chemistry Letters},
number = 18,
volume = 8,
place = {United States},
year = 2017,
month = 9
}
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