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Cis–trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel

Overview of attention for article published in Nature, November 2005
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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 (81st percentile)
  • Average Attention Score compared to outputs of the same age and source

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3 patents
1 Wikipedia page
1 research highlight platform


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300 Mendeley
1 CiteULike
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Cis–trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel
Published in
Nature, November 2005
DOI 10.1038/nature04130
Pubmed ID

Sarah C. R. Lummis, Darren L. Beene, Lori W. Lee, Henry A. Lester, R. William Broadhurst, Dennis A. Dougherty


5-hydroxytryptamine type 3 (5-HT3) receptors are members of the Cys-loop receptor superfamily. Neurotransmitter binding in these proteins triggers the opening (gating) of an ion channel by means of an as-yet-uncharacterized conformational change. Here we show that a specific proline (Pro 8*), located at the apex of the loop between the second and third transmembrane helices (M2-M3), can link binding to gating through a cis-trans isomerization of the protein backbone. Using unnatural amino acid mutagenesis, a series of proline analogues with varying preference for the cis conformer was incorporated at the 8* position. Proline analogues that strongly favour the trans conformer produced non-functional channels. Among the functional mutants there was a strong correlation between the intrinsic cis-trans energy gap of the proline analogue and the activation of the channel, suggesting that cis-trans isomerization of this single proline provides the switch that interconverts the open and closed states of the channel. Consistent with this proposal, nuclear magnetic resonance studies on an M2-M3 loop peptide reveal two distinct, structured forms. Our results thus confirm the structure of the M2-M3 loop and the critical role of Pro 8* in the 5-HT3 receptor. In addition, they suggest that a molecular rearrangement at Pro 8* is the structural mechanism that opens the receptor pore.

Mendeley readers

The data shown below were compiled from readership statistics for 300 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 10 3%
United Kingdom 4 1%
Germany 4 1%
Canada 2 <1%
Switzerland 2 <1%
Belgium 1 <1%
Chile 1 <1%
Austria 1 <1%
Spain 1 <1%
Other 2 <1%
Unknown 272 91%

Demographic breakdown

Readers by professional status Count As %
Researcher 90 30%
Student > Ph. D. Student 72 24%
Student > Master 27 9%
Student > Bachelor 23 8%
Professor > Associate Professor 19 6%
Other 52 17%
Unknown 17 6%
Readers by discipline Count As %
Agricultural and Biological Sciences 115 38%
Chemistry 93 31%
Biochemistry, Genetics and Molecular Biology 28 9%
Physics and Astronomy 10 3%
Neuroscience 10 3%
Other 19 6%
Unknown 25 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 26 November 2019.
All research outputs
of 16,275,174 outputs
Outputs from Nature
of 76,759 outputs
Outputs of similar age
of 15,217,963 outputs
Outputs of similar age from Nature
of 75,793 outputs
Altmetric has tracked 16,275,174 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 76,759 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 87.8. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
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 15,217,963 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 81% of its contemporaries.
We're also able to compare this research output to 75,793 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.