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

J 2017

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

KREPL, Miroslav; Markus BLATTER; Antoine CLERY; Fred F DAMBERGER; Frederic H T ALLAIN et. al.

Základní údaje

Originální název

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

Autoři

KREPL, Miroslav; Markus BLATTER; Antoine CLERY; Fred F DAMBERGER; Frederic H T ALLAIN a Jiří ŠPONER

Vydání

Nucleic acids research, Oxford University Press, 2017, 1362-4962

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

DOI

https://doi.org/10.1093/nar/gkx418

UT WoS

000406776400049

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 6. 2017 16:44, RNDr. Miroslav Krepl, Ph.D.

Anotace

V originále

The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 A 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 and interpreting the hydration patterns of protein/RNA complexes. Hydration is not easily detectable in NMR experiments but can affect stability of protein/RNA complexes.

Citovat

KREPL, Miroslav; Markus BLATTER; Antoine CLERY; Fred F DAMBERGER; Frederic H T ALLAIN a Jiří ŠPONER. Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition. Nucleic acids research. Oxford University Press, 2017. ISSN 1362-4962. Dostupné z: https://doi.org/10.1093/nar/gkx418.

@article{1382663,
   author = {Krepl, Miroslav and Blatter, Markus and Clery, Antoine and Damberger, Fred F and Allain, Frederic H T and Šponer, Jiří},
   doi = {https://doi.org/10.1093/nar/gkx418},
   issn = {1362-4962},
   journal = {Nucleic acids research},
   title = {Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition.},
   url = {http://dx.doi.org/10.1093/nar/gkx418},
   year = {2017}
}

TY  - JOUR
ID  - 1382663
AU  - Krepl, Miroslav - Blatter, Markus - Clery, Antoine - Damberger, Fred F - Allain, Frederic H T - Šponer, Jiří
PY  - 2017
TI  - Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition.
JF  - Nucleic acids research
PB  - Oxford University Press
SN  - 13624962
UR  - http://dx.doi.org/10.1093/nar/gkx418
L2  - http://dx.doi.org/10.1093/nar/gkx418
N2  - The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 A 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 and interpreting the hydration patterns of protein/RNA complexes. Hydration is not easily detectable in NMR experiments but can affect stability of protein/RNA complexes.
ER  -

KREPL, Miroslav; Markus BLATTER; Antoine CLERY; Fred F DAMBERGER; Frederic H T ALLAIN a Jiří ŠPONER. Structural study of the Fox-1 RRM protein hydration reveals a role for key water molecules in RRM-RNA recognition. \textit{Nucleic acids research}. Oxford University Press, 2017. ISSN~1362-4962. Dostupné z: https://doi.org/10.1093/nar/gkx418.

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