Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch
Abstract
The widespread Mn2+-sensing yybP-ykoY riboswitch controls the expression of bacterial Mn2+ homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch aptamer from Xanthomonas oryzae at 2.96 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 µs of MD simulations, we observe that loss of divalents from the core triggers local structural perturbations in the adjacent docking interface, laying the foundation for signal transduction to the regulatory switch helix. Using single-molecule FRET, we unveil a previously unobserved extended 4WJ conformation that samples transient docked states in the presence of Mg2+. Only upon adding sub-millimolar Mn2+, however, can the 4WJ dock stably, a feature lost upon mutation of an adenosine contacting Mn2+ in the core. These observations illuminate how subtly differing ligand preferences of competing metal ions become amplified by the coupling of local with global RNA dynamics.
- Authors:
-
[1];
[2];
[3];
[3];
[3];
[2];
[1]
- Univ. of Michigan, Ann Arbor, MI (United States)
- Cornell Univ., Ithaca, NY (United States)
- Czech Academy of Sciences (CAS), Brno (Czech Republic). Institute of Biophysics; Palacky University, Olomouc (Czech Republic)
- Palacky University, Olomouc (Czech Republic)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Institutes of Health (NIH); Grant Agency of the Czech Republic
- OSTI Identifier:
- 1574155
- Grant/Contract Number:
- AC02-06CH11357; GM062357; GM118524; GM118174; 18-25349S; P30 GM124165; S10 RR029205
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; molecular conformation; riboswitches; single-molecule biophysics
Citation Formats
Suddala, Krishna C., Price, Ian R., Dandpat, Shiba S., Janeček, Michal, Kührová, Petra, Šponer, Jiří, Banáš, Pavel, Ke, Ailong, and Walter, Nils G. Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch. United States: N. p., 2019.
Web. doi:10.1038/s41467-019-12230-5.
Suddala, Krishna C., Price, Ian R., Dandpat, Shiba S., Janeček, Michal, Kührová, Petra, Šponer, Jiří, Banáš, Pavel, Ke, Ailong, & Walter, Nils G. Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch. United States. https://doi.org/10.1038/s41467-019-12230-5
Suddala, Krishna C., Price, Ian R., Dandpat, Shiba S., Janeček, Michal, Kührová, Petra, Šponer, Jiří, Banáš, Pavel, Ke, Ailong, and Walter, Nils G. Fri .
"Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch". United States. https://doi.org/10.1038/s41467-019-12230-5. https://www.osti.gov/servlets/purl/1574155.
@article{osti_1574155,
title = {Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch},
author = {Suddala, Krishna C. and Price, Ian R. and Dandpat, Shiba S. and Janeček, Michal and Kührová, Petra and Šponer, Jiří and Banáš, Pavel and Ke, Ailong and Walter, Nils G.},
abstractNote = {The widespread Mn2+-sensing yybP-ykoY riboswitch controls the expression of bacterial Mn2+ homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch aptamer from Xanthomonas oryzae at 2.96 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 µs of MD simulations, we observe that loss of divalents from the core triggers local structural perturbations in the adjacent docking interface, laying the foundation for signal transduction to the regulatory switch helix. Using single-molecule FRET, we unveil a previously unobserved extended 4WJ conformation that samples transient docked states in the presence of Mg2+. Only upon adding sub-millimolar Mn2+, however, can the 4WJ dock stably, a feature lost upon mutation of an adenosine contacting Mn2+ in the core. These observations illuminate how subtly differing ligand preferences of competing metal ions become amplified by the coupling of local with global RNA dynamics.},
doi = {10.1038/s41467-019-12230-5},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {Fri Sep 20 00:00:00 EDT 2019},
month = {Fri Sep 20 00:00:00 EDT 2019}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 13 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview
journal, January 2018
- Šponer, Jiří; Bussi, Giovanni; Krepl, Miroslav
- Chemical Reviews, Vol. 118, Issue 8
Model-Based Fitting of Single-Channel Dwell-Time Distributions
journal, September 2004
- Qin, Feng; Li, Ling
- Biophysical Journal, Vol. 87, Issue 3
Single-molecule enzymology of RNA: Essential functional groups impact catalysis from a distance
journal, June 2004
- Rueda, D.; Bokinsky, G.; Rhodes, M. M.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 27
Correlating Structural Dynamics and Function in Single Ribozyme Molecules
journal, May 2002
- Zhuang, X.
- Science, Vol. 296, Issue 5572
Long-Range Interactions in Riboswitch Control of Gene Expression
journal, May 2017
- Jones, Christopher P.; Ferré-D'Amaré, Adrian R.
- Annual Review of Biophysics, Vol. 46, Issue 1
Multiple Metal-Binding Cores Are Required for Metalloregulation by M-box Riboswitch RNAs
journal, September 2009
- Wakeman, Catherine A.; Ramesh, Arati; Winkler, Wade C.
- Journal of Molecular Biology, Vol. 392, Issue 3
The role of nucleobase interactions in RNA structure and dynamics
journal, October 2014
- Bottaro, Sandro; Di Palma, Francesco; Bussi, Giovanni
- Nucleic Acids Research, Vol. 42, Issue 21
The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in Gram-positive bacteria
journal, November 1998
- Grundy, Frank J.; Henkin, Tina M.
- Molecular Microbiology, Vol. 30, Issue 4
Solving novel RNA structures using only secondary structural fragments
journal, October 2010
- Robertson, Michael P.; Chi, Young-In; Scott, William G.
- Methods, Vol. 52, Issue 2
The Ubiquitous yybP-ykoY Riboswitch Is a Manganese-Responsive Regulatory Element
journal, March 2015
- Dambach, Michael; Sandoval, Melissa; Updegrove, Taylor B.
- Molecular Cell, Vol. 57, Issue 6
Structural analysis of a class III preQ 1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics
journal, June 2015
- Liberman, Joseph A.; Suddala, Krishna C.; Aytenfisu, Asaminew
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 27
Metalloriboswitches: RNA-based inorganic ion sensors that regulate genes
journal, April 2017
- Wedekind, Joseph E.; Dutta, Debapratim; Belashov, Ivan A.
- Journal of Biological Chemistry, Vol. 292, Issue 23
Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012
- Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald
journal, August 2013
- Salomon-Ferrer, Romelia; Götz, Andreas W.; Poole, Duncan
- Journal of Chemical Theory and Computation, Vol. 9, Issue 9
Single-molecule imaging of non-equilibrium molecular ensembles on the millisecond timescale
journal, February 2016
- Juette, Manuel F.; Terry, Daniel S.; Wasserman, Michael R.
- Nature Methods, Vol. 13, Issue 4
Structure and Mechanism of a Metal-Sensing Regulatory RNA
journal, September 2007
- Dann, Charles E.; Wakeman, Catherine A.; Sieling, Cecelia L.
- Cell, Vol. 130, Issue 5
Implications of molecular heterogeneity for the cooperativity of biological macromolecules
journal, May 2011
- Solomatin, Sergey V.; Greenfeld, Max; Herschlag, Daniel
- Nature Structural & Molecular Biology, Vol. 18, Issue 6
Riboswitch diversity and distribution
journal, April 2017
- McCown, Phillip J.; Corbino, Keith A.; Stav, Shira
- RNA, Vol. 23, Issue 7
Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
journal, May 2009
- Terwilliger, Thomas C.; Adams, Paul D.; Read, Randy J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 6
Ligand-modulated folding of the full-length adenine riboswitch probed by NMR and single-molecule FRET spectroscopy
journal, February 2017
- Warhaut, Sven; Mertinkus, Klara Rebecca; Höllthaler, Philipp
- Nucleic Acids Research, Vol. 45, Issue 9
Enthalpy-Driven RNA Folding: Single-Molecule Thermodynamics of Tetraloop−Receptor Tertiary Interaction †
journal, March 2009
- Fiore, Julie L.; Kraemer, Benedikt; Koberling, Felix
- Biochemistry, Vol. 48, Issue 11
Multiple native states reveal persistent ruggedness of an RNA folding landscape
journal, February 2010
- Solomatin, Sergey V.; Greenfeld, Max; Chu, Steven
- Nature, Vol. 463, Issue 7281
The T box mechanism: tRNA as a regulatory molecule
journal, November 2009
- Green, Nicholas J.; Grundy, Frank J.; Henkin, Tina M.
- FEBS Letters, Vol. 584, Issue 2
Mn2+-Sensing Mechanisms of yybP-ykoY Orphan Riboswitches
journal, March 2015
- Price, Ian R.; Gaballa, Ahmed; Ding, Fang
- Molecular Cell, Vol. 57, Issue 6
The shape-shifting quasispecies of RNA: one sequence, many functional folds
journal, January 2011
- Marek, Matthew S.; Johnson-Buck, Alexander; Walter, Nils G.
- Physical Chemistry Chemical Physics, Vol. 13, Issue 24
Identification and functional characterization of small non-coding RNAs in Xanthomonas oryzae pathovar oryzae
journal, January 2011
- Liang, Hong; Zhao, Ying-Tao; Zhang, Jie-Qiong
- BMC Genomics, Vol. 12, Issue 1
RNA structure comparison, motif search and discovery using a reduced representation of RNA conformational space
journal, August 2003
- Duarte, C. M.
- Nucleic Acids Research, Vol. 31, Issue 16
A rugged free energy landscape separates multiple functional RNA folds throughout denaturation
journal, November 2008
- Ditzler, Mark A.; Rueda, David; Mo, Jingjie
- Nucleic Acids Research, Vol. 36, Issue 22
Novel small RNA-encoding genes in the intergenic regions of Escherichia coli
journal, June 2001
- Argaman, Liron; Hershberg, Ruth; Vogel, Jörg
- Current Biology, Vol. 11, Issue 12
T7 RNA polymerase produces 5′ end heterogeneity during in vitro transcription from certain templates
journal, October 1998
- Pleiss, Jeffrey A.; Derrick, Maria L.; Uhlenbeck, Olke C.
- RNA, Vol. 4, Issue 10
Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent
journal, May 2013
- Li, Pengfei; Roberts, Benjamin P.; Chakravorty, Dhruva K.
- Journal of Chemical Theory and Computation, Vol. 9, Issue 6
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Gene regulation by riboswitches
journal, June 2004
- Mandal, Maumita; Breaker, Ronald R.
- Nature Reviews Molecular Cell Biology, Vol. 5, Issue 6
Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers
journal, June 2007
- Pérez, Alberto; Marchán, Iván; Svozil, Daniel
- Biophysical Journal, Vol. 92, Issue 11
Performance of Molecular Mechanics Force Fields for RNA Simulations: Stability of UUCG and GNRA Hairpins
journal, November 2010
- Banáš, Pavel; Hollas, Daniel; Zgarbová, Marie
- Journal of Chemical Theory and Computation, Vol. 6, Issue 12
A Novel Manganese Efflux System, YebN, Is Required for Virulence by Xanthomonas oryzae pv. oryzae
journal, July 2011
- Li, Chunxia; Tao, Jun; Mao, Daqing
- PLoS ONE, Vol. 6, Issue 7
Riboswitches in eubacteria sense the second messenger c-di-AMP
journal, October 2013
- Nelson, James W.; Sudarsan, Narasimhan; Furukawa, Kazuhiro
- Nature Chemical Biology, Vol. 9, Issue 12
Removal of Covalent Heterogeneity Reveals Simple Folding Behavior for P4-P6 RNA
journal, April 2011
- Greenfeld, Max; Solomatin, Sergey V.; Herschlag, Daniel
- Journal of Biological Chemistry, Vol. 286, Issue 22
New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control
journal, April 2004
- Barrick, J. E.; Corbino, K. A.; Winkler, W. C.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 17
Convergent Use of Heptacoordination for Cation Selectivity by RNA and Protein Metalloregulators
journal, August 2018
- Bachas, Sharrol T.; Ferré-D'Amaré, Adrian R.
- Cell Chemical Biology, Vol. 25, Issue 8
Refinement of the Cornell et al. Nucleic Acids Force Field Based on Reference Quantum Chemical Calculations of Glycosidic Torsion Profiles
journal, August 2011
- Zgarbová, Marie; Otyepka, Michal; Šponer, Jiří
- Journal of Chemical Theory and Computation, Vol. 7, Issue 9
The Shine-Dalgarno sequence of riboswitch-regulated single mRNAs shows ligand-dependent accessibility bursts
journal, January 2016
- Rinaldi, Arlie J.; Lund, Paul E.; Blanco, Mario R.
- Nature Communications, Vol. 7, Issue 1
A Decade of Riboswitches
journal, January 2013
- Serganov, Alexander; Nudler, Evgeny
- Cell, Vol. 152, Issue 1-2
The non-Watson-Crick base pairs and their associated isostericity matrices
journal, August 2002
- Leontis, N. B.
- Nucleic Acids Research, Vol. 30, Issue 16
Molecular Dynamics and Quantum Mechanics of RNA: Conformational and Chemical Change We Can Believe In
journal, January 2010
- Ditzler, Mark A.; Otyepka, Michal; Šponer, Jiřì
- Accounts of Chemical Research, Vol. 43, Issue 1
Bacterial Riboswitches Cooperatively Bind Ni 2+ or Co 2+ Ions and Control Expression of Heavy Metal Transporters
journal, March 2015
- Furukawa, Kazuhiro; Ramesh, Arati; Zhou, Zhiyuan
- Molecular Cell, Vol. 57, Issue 6
Single-Molecule FRET Kinetics of the Mn 2+ Riboswitch: Evidence for Allosteric Mg 2+ Control of “Induced-Fit” vs “Conformational Selection” Folding Pathways
journal, February 2019
- Sung, Hsuan-Lei; Nesbitt, David J.
- The Journal of Physical Chemistry B, Vol. 123, Issue 9
Structural basis of ligand binding by a c-di-GMP riboswitch
journal, November 2009
- Smith, Kathryn D.; Lipchock, Sarah V.; Ames, Tyler D.
- Nature Structural & Molecular Biology, Vol. 16, Issue 12
Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations
journal, July 2008
- Joung, In Suk; Cheatham, Thomas E.
- The Journal of Physical Chemistry B, Vol. 112, Issue 30
Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities Are Intrinsic
journal, October 2004
- Okumus, Burak; Wilson, Timothy J.; Lilley, David M. J.
- Biophysical Journal, Vol. 87, Issue 4
Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP
journal, July 2008
- Sudarsan, N.; Lee, E. R.; Weinberg, Z.
- Science, Vol. 321, Issue 5887
The missing term in effective pair potentials
journal, November 1987
- Berendsen, H. J. C.; Grigera, J. R.; Straatsma, T. P.
- The Journal of Physical Chemistry, Vol. 91, Issue 24
Magnesium Ion–Water Coordination and Exchange in Biomolecular Simulations
journal, March 2012
- Allnér, Olof; Nilsson, Lennart; Villa, Alessandra
- Journal of Chemical Theory and Computation, Vol. 8, Issue 4
VMD: Visual molecular dynamics
journal, February 1996
- Humphrey, William; Dalke, Andrew; Schulten, Klaus
- Journal of Molecular Graphics, Vol. 14, Issue 1
Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression
journal, October 2002
- Winkler, Wade; Nahvi, Ali; Breaker, Ronald R.
- Nature, Vol. 419, Issue 6910