Title: Entropic control of the free-energy landscape of an archetypal biomolecular machine

Abstract

Biomolecular machines are complex macromolecular assemblies that utilize thermal and chemical energy to perform essential, multistep, cellular processes. Despite possessing different architectures and functions, an essential feature of the mechanisms of action of all such machines is that they require dynamic rearrangements of structural components. Surprisingly, biomolecular machines generally possess only a limited set of such motions, suggesting that these dynamics must be repurposed to drive different mechanistic steps. Although ligands that interact with these machines are known to drive such repurposing, the physical and structural mechanisms through which ligands achieve this remain unknown. Using temperature-dependent, single-molecule measurements analyzed with a time-resolution-enhancing algorithm, here, we dissect the free-energy landscape of an archetypal biomolecular machine, the bacterial ribosome, to reveal how its dynamics are repurposed to drive distinct steps during ribosome-catalyzed protein synthesis. Specifically, we show that the free-energy landscape of the ribosome encompasses a network of allosterically coupled structural elements that coordinates the motions of these elements. Moreover, we reveal that ribosomal ligands which participate in disparate steps of the protein synthesis pathway repurpose this network by differentially modulating the structural flexibility of the ribosomal complex (i.e., the entropic component of the free-energy landscape). We propose that such ligand-dependent entropicmore » control of free-energy landscapes has evolved as a general strategy through which ligands may regulate the functions of all biomolecular machines. Such entropic control is therefore an important driver in the evolution of naturally occurring biomolecular machines and a critical consideration for the design of synthetic molecular machines.« less

Authors:

Ray, Korak Kumar  ^[1];

• Search DOE PAGES for author "Ray, Korak Kumar"
• Search DOE PAGES for ORCID "0000-0001-5390-698X"

Kinz-Thompson, Colin D.  ^[1];

• Search DOE PAGES for author "Kinz-Thompson, Colin D."
• Search DOE PAGES for ORCID "0000-0002-2636-7893"

Fei, Jingyi  ^[1];

• Search DOE PAGES for author "Fei, Jingyi"
• Search DOE PAGES for ORCID "0000-0002-9775-3820"

Wang, Bin ^[2]; Lin, Qiao ^[2]; Gonzalez, Ruben L.  ^[1]

• Search DOE PAGES for author "Gonzalez, Ruben L."
• Search DOE PAGES for ORCID "0000-0002-1344-5581"

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+ Show Author Affiliations

1. Department of Chemistry, Columbia University, New York, NY 10027
2. Department of Mechanical Engineering, Columbia University, New York, NY 10027

Publication Date:

Mon May 15 00:00:00 EDT 2023

Sponsoring Org.:

USDOE

OSTI Identifier:

1973697

Grant/Contract Number:  

AC05-06OR23100

Resource Type:

Published Article

Journal Name:

Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:

Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 120 Journal Issue: 21; Journal ID: ISSN 0027-8424

Publisher:

Proceedings of the National Academy of Sciences

Country of Publication:

United States

Language:

English