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Structural Dynamics of the GW182 Silencing Domain Including its RNA Recognition motif (RRM) Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry

Overview of attention for article published in Journal of the American Society for Mass Spectrometry, October 2017
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Title
Structural Dynamics of the GW182 Silencing Domain Including its RNA Recognition motif (RRM) Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry
Published in
Journal of the American Society for Mass Spectrometry, October 2017
DOI 10.1007/s13361-017-1830-9
Pubmed ID
Authors

Maja K. Cieplak-Rotowska, Krzysztof Tarnowski, Marcin Rubin, Marc R. Fabian, Nahum Sonenberg, Michal Dadlez, Anna Niedzwiecka

Abstract

The human GW182 protein plays an essential role in micro(mi)RNA-dependent gene silencing. miRNA silencing is mediated, in part, by a GW182 C-terminal region called the silencing domain, which interacts with the poly(A) binding protein and the CCR4-NOT deadenylase complex to repress protein synthesis. Structural studies of this GW182 fragment are challenging due to its predicted intrinsically disordered character, except for its RRM domain. However, detailed insights into the properties of proteins containing disordered regions can be provided by hydrogen-deuterium exchange mass spectrometry (HDX/MS). In this work, we applied HDX/MS to define the structural state of the GW182 silencing domain. HDX/MS analysis revealed that this domain is clearly divided into a natively unstructured part, including the CCR4-NOT interacting motif 1, and a distinct RRM domain. The GW182 RRM has a very dynamic structure, since water molecules can penetrate the whole domain in 2 h. The finding of this high structural dynamics sheds new light on the RRM structure. Though this domain is one of the most frequently occurring canonical protein domains in eukaryotes, these results are - to our knowledge - the first HDX/MS characteristics of an RRM. The HDX/MS studies show also that the α2 helix of the RRM can display EX1 behavior after a freezing-thawing cycle. This means that the RRM structure is sensitive to environmental conditions and can change its conformation, which suggests that the state of the RRM containing proteins should be checked by HDX/MS in regard of the conformational uniformity. Graphical Abstract.

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Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 32%
Researcher 6 27%
Professor 1 5%
Other 1 5%
Lecturer 1 5%
Other 1 5%
Unknown 5 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 32%
Agricultural and Biological Sciences 4 18%
Chemistry 2 9%
Computer Science 1 5%
Environmental Science 1 5%
Other 2 9%
Unknown 5 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 October 2017.
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#22,764,772
of 25,382,440 outputs
Outputs from Journal of the American Society for Mass Spectrometry
#3,431
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Outputs of similar age
#297,922
of 339,185 outputs
Outputs of similar age from Journal of the American Society for Mass Spectrometry
#41
of 51 outputs
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