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Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity

Overview of attention for article published in PLOS ONE, February 2013
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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1 blog
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Citations

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121 Dimensions

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Title
Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity
Published in
PLOS ONE, February 2013
DOI 10.1371/journal.pone.0057008
Pubmed ID
Authors

Meng-Chiao Ho, Carola Wilczek, Jeffrey B. Bonanno, Li Xing, Janina Seznec, Tsutomu Matsui, Lester G. Carter, Takashi Onikubo, P. Rajesh Kumar, Man K. Chan, Michael Brenowitz, R. Holland Cheng, Ulf Reimer, Steven C. Almo, David Shechter

Abstract

The arginine methyltransferase PRMT5-MEP50 is required for embryogenesis and is misregulated in many cancers. PRMT5 targets a wide variety of substrates, including histone proteins involved in specifying an epigenetic code. However, the mechanism by which PRMT5 utilizes MEP50 to discriminate substrates and to specifically methylate target arginines is unclear. To test a model in which MEP50 is critical for substrate recognition and orientation, we determined the crystal structure of Xenopus laevis PRMT5-MEP50 complexed with S-adenosylhomocysteine (SAH). PRMT5-MEP50 forms an unusual tetramer of heterodimers with substantial surface negative charge. MEP50 is required for PRMT5-catalyzed histone H2A and H4 methyltransferase activity and binds substrates independently. The PRMT5 catalytic site is oriented towards the cross-dimer paired MEP50. Histone peptide arrays and solution assays demonstrate that PRMT5-MEP50 activity is inhibited by substrate phosphorylation and enhanced by substrate acetylation. Electron microscopy and reconstruction showed substrate centered on MEP50. These data support a mechanism in which MEP50 binds substrate and stimulates PRMT5 activity modulated by substrate post-translational modifications.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 122 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 2%
Japan 1 <1%
United Kingdom 1 <1%
Unknown 118 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 34 28%
Researcher 27 22%
Student > Master 11 9%
Student > Bachelor 11 9%
Student > Doctoral Student 6 5%
Other 16 13%
Unknown 17 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 38 31%
Agricultural and Biological Sciences 37 30%
Chemistry 20 16%
Medicine and Dentistry 7 6%
Psychology 2 2%
Other 3 2%
Unknown 15 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 23 August 2018.
All research outputs
#3,102,958
of 22,699,621 outputs
Outputs from PLOS ONE
#40,778
of 193,796 outputs
Outputs of similar age
#26,606
of 193,194 outputs
Outputs of similar age from PLOS ONE
#936
of 5,363 outputs
Altmetric has tracked 22,699,621 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 193,796 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 193,194 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 5,363 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.