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Title: The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domain 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.
Authors:
 [1] ; ORCiD logo [1] ;  [2]
  1. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry
  2. Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry; Univ. of Illinois, Urbana-Champaign, IL (United States). Center for the Physics of Living Cells; Univ. of Illinois, Urbana-Champaign, IL (United States). Beckman Inst.; Univ. of Illinois, Urbana-Champaign, IL (United States). Carl Woese Inst. for Genomic Biology
Publication Date:
Grant/Contract Number:
SC0005435; R01GM116961
Type:
Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 56; Journal Issue: 45; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Research Org:
Univ. of Illinois at Urbana-Champaign, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1410674

Lai, Jonathan, Ghaemi, Zhaleh, and Luthey-Schulten, Zaida. The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains. United States: N. p., Web. doi:10.1021/acs.biochem.7b00591.
Lai, Jonathan, Ghaemi, Zhaleh, & Luthey-Schulten, Zaida. The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains. United States. doi:10.1021/acs.biochem.7b00591.
Lai, Jonathan, Ghaemi, Zhaleh, and Luthey-Schulten, Zaida. 2017. "The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains". United States. doi:10.1021/acs.biochem.7b00591. https://www.osti.gov/servlets/purl/1410674.
@article{osti_1410674,
title = {The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains},
author = {Lai, Jonathan and Ghaemi, Zhaleh and Luthey-Schulten, Zaida},
abstractNote = {Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- and post-hydrolysis structures through two distinct pathways. Here, we show that the transition free energy is minimal along a non-intuitive pathway that involves “separation” of the GTP binding domain (domain 1) from the OB folds (domains 2 and 3), followed by domain 1 rotation, and, eventually, locking the EF-Tu conformation in the post-hydrolysis state. The domain separation also leads to a slight extension of the linker connecting domain 1 to domain 2. Using docking tools and correlation-based analysis, we identified and characterized the EF-Tu conformations that release the tRNA. These calculations suggest that EF-Tu can release the tRNA before the domains separate and after domain 1 rotates by 25°. Lastly, we also examined the EF-Tu conformations in the context of the ribosome. Given the high degrees of sequence similarity with other translational GTPases, we predict a similar separation mechanism is followed.},
doi = {10.1021/acs.biochem.7b00591},
journal = {Biochemistry},
number = 45,
volume = 56,
place = {United States},
year = {2017},
month = {10}
}