Crystal structure of Escherichia coli thiamine pyrophosphate-sensing riboswitch in the apo state

Lee, Hyun Kyung; Lee, Yun-Tzai; Fan, Lixin; Wilt, Haley M.; Conrad, Chelsie E.; Yu, Ping; Zhang, Jinwei; Shi, Genbin; Ji, Xinhua; Wang, Yun-Xing; Stagno, Jason R.

doi:10.1016/j.str.2023.05.003

Crystal structure of Escherichia coli thiamine pyrophosphate-sensing riboswitch in the apo state

Journal Article · Mon May 29 00:00:00 EDT 2023 · Structure

DOI:https://doi.org/10.1016/j.str.2023.05.003· OSTI ID:2423353

Lee, Hyun Kyung ^[1]; Lee, Yun-Tzai ^[1]; Fan, Lixin ^[2]; Wilt, Haley M. ^[1]; Conrad, Chelsie E. ^[3]; Yu, Ping ^[1]; ^[4]; Shi, Genbin ^[1]; Ji, Xinhua ^[1]; Wang, Yun-Xing ^[1]; ^[1]

National Cancer Institute, Frederick, MD (United States)
Frederick National Laboratory for Cancer Research, MD (United States)
National Cancer Institute, Frederick, MD (United States); University of Utah, Salt Lake City, UT (United States)
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States)

The thiamine pyrophosphate (TPP)-sensing riboswitch is one of the earliest discovered and most widespread riboswitches. Numerous structural studies have been reported for this riboswitch bound with various ligands. However, the ligand-free (apo) structure remains unknown. Here, we report a 3.1 Å resolution crystal structure of Escherichia coli TPP riboswitch in the apo state, which exhibits an extended, Y-shaped conformation further supported by small-angle X-ray scattering data and driven molecular dynamics simulations. The loss of ligand interactions results in helical uncoiling of P5 and disruption of the key tertiary interaction between the sensory domains. Opening of the aptamer propagates to the gene-regulatory P1 helix and generates the key conformational flexibility needed for the switching behavior. Much of the ligand-binding site at the three-way junction is unaltered, thereby maintaining a partially preformed pocket. Together, these results paint a dynamic picture of the ligand-induced conformational changes in TPP riboswitches that confer conditional gene regulation.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423353

Journal Information:: Structure, Journal Name: Structure Journal Issue: 7 Vol. 31; ISSN 0969-2126

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry
Biophysics
Cell Biology
Molecular Biology
RNA structure
X-ray crystallography
X-ray scattering
apo conformation
aptamer
molecular dynamics
riboswitch
thiamine pyrophosphate

Crystal structure of Escherichia coli thiamine pyrophosphate-sensing riboswitch in the apo state

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