Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition

Nucleic Acids Research
Miroslav KreplJirí Sponer

Abstract

The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 Å X-ray structure of the free Fox-1 containing six distinct monomers. We use this and the nuclear magnetic resonance (NMR) structure of the Fox-1 protein/RNA complex for molecular dynamics (MD) analyses of the structured hydration. The individual monomers of the X-ray structure show diverse hydration patterns, however, MD excellently reproduces the most occupied hydration sites. Simulations of the protein/RNA complex show hydration consistent with the isolated protein complemented by hydration sites specific to the protein/RNA interface. MD predicts intricate hydration sites with water-binding times extending up to hundreds of nanoseconds. We characterize two of them using NMR spectroscopy, RNA binding with switchSENSE and free-energy calculations of mutant proteins. Both hydration sites are experimentally confirmed and their abolishment reduces the binding free-energy. A quantitative agreement between theory and experiment is achieved for the S155A substitution but not for the S122A mutant. The S155 hydration site is evolutionarily conserved within the RRM domains. In conclusion, MD is an effective tool for predicting...Continue Reading

References

Jan 1, 1988·Annual Review of Biophysics and Biophysical Chemistry·E Westhof
Aug 5, 1988·Journal of Molecular Biology·N ThankiJ M Goodfellow
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 1, 1995·Proteins·D Frishman, P Argos
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·O Carugo, P Argos
Jul 25, 2000·Journal of Molecular Biology·P Auffinger, E Westhof
Oct 14, 2000·Annual Review of Physical Chemistry·T E Cheatham, P A Kollman
May 26, 2001·Acta Crystallographica. Section D, Biological Crystallography·U DasS J Wodak
Feb 28, 2002·Nucleic Acids Research·Zdenek MorávekBohdan Schneider
May 14, 2004·Annual Review of Biophysics and Biomolecular Structure·B Jayaram, Tarun Jain
Nov 2, 2005·Molecular and Cellular Biology·Jason G UnderwoodDouglas L Black
Dec 20, 2005·The EMBO Journal·Sigrid D AuweterFrédéric H-T Allain
Apr 18, 2006·Biophysical Journal·Maryna V KrasovskaJirí Sponer
Aug 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Maria M RhodesNils G Walter
Apr 25, 2007·Nucleic Acids Research·Ian W DavisDavid C Richardson
Jun 19, 2007·Current Opinion in Structural Biology·Pascal Auffinger, Yaser Hashem
Aug 2, 2007·EMBO Reports·Aura M TintaruStuart A Wilson
Dec 11, 2007·The Journal of Chemical Physics·Thomas SteinbrecherDavid A Case
Dec 22, 2007·Chemical Reviews·Philip Ball
Jun 3, 2008·Current Opinion in Structural Biology·Antoine CléryFrédéric H-T Allain
Jul 3, 2008·The Journal of Physical Chemistry. B·In Suk Joung, Thomas E Cheatham
Oct 22, 2008·Methods : a Companion to Methods in Enzymology·Yaser Hashem, Pascal Auffinger
Jun 26, 2009·Nucleic Acids Research·Kengo TsudaShigeyuki Yokoyama
Sep 17, 2009·Accounts of Chemical Research·Mark A DitzlerNils G Walter
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Oct 12, 2010·Nucleic Acids Research·Kengo TsudaYutaka Muto
Jan 19, 2011·Progress in Nuclear Magnetic Resonance Spectroscopy·Cyril DominguezFrédéric H-T Allain

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Citations

Mar 22, 2018·Physical Chemistry Chemical Physics : PCCP·Tomohiko HayashiMasahiro Kinoshita
Jul 14, 2018·Journal of Molecular Modeling·Juan David Ospina-VillaAbsalom Zamorano-Carrillo
Aug 6, 2019·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Giorgio Schirò, Martin Weik
Apr 10, 2019·Nature Communications·Polina DenichenkoRotem Karni
Apr 16, 2021·The Journal of Biological Chemistry·Miroslav KreplJiri Sponer
Jan 4, 2018·Chemical Reviews·Jiří ŠponerMichal Otyepka
Oct 17, 2017·Journal of Chemical Theory and Computation·Pavlína PokornáJiří Šponer
May 6, 2019·Journal of Chemical Theory and Computation·Andrea CesariGiovanni Bussi
Dec 20, 2018·The Journal of Physical Chemistry. B·Sara CapponiMatthias Heyden
Oct 29, 2021·Biophysical Journal·Lev Levintov, Harish Vashisth

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Methods Mentioned

BETA
X-ray
nuclear magnetic resonance
NMR
chips
Biosensors
chip
Surface Plasmon Resonance
amide resonance

Software Mentioned

ff12SB
PROCHECK
VMD
AMBER
Raster3D
- Rosetta
switchANALYSIS
ATNOS
DSSP
Phenix

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