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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485635" target="_blank" >RIV/68081707:_____/17:00485635 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73584551

Result on the web

<a href="http://dx.doi.org/10.1093/nar/gkx418" target="_blank" >http://dx.doi.org/10.1093/nar/gkx418</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkx418" target="_blank" >10.1093/nar/gkx418</a>

Result language

angličtina

Original language name

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

Original language description

The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 angstrom X-ray structure of the free Fox-1 containing six distinct monomers. We use this and the nuclear magnetic resonance (NMR) structure of the Fox1 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

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Volume of the periodical

45

Issue of the periodical within the volume

13

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

8046-8063

UT code for WoS article

000406776400049

EID of the result in the Scopus database

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