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

Lai, Jonathan; Ghaemi, Zhaleh; Luthey-Schulten, Zaida

doi:10.1021/acs.biochem.7b00591

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

Journal Article · Wed Oct 18 00:00:00 EDT 2017 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.7b00591· OSTI ID:1410674

Lai, Jonathan ^[1]; ^[2]; Luthey-Schulten, Zaida ^[3]

Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry; University of Illinois at Urbana-Champaign
Univ. of Illinois, Urbana-Champaign, IL (United States). Dept. of Chemistry
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

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.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Illinois, Champaign, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)

Grant/Contract Number:: SC0005435

OSTI ID:: 1410674

Journal Information:: Biochemistry, Journal Name: Biochemistry Journal Issue: 45 Vol. 56; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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