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Quantifying conformational changes in GPCRs: glimpse of a common functional mechanism

Overview of attention for article published in BMC Bioinformatics, April 2015
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  • Above-average Attention Score compared to outputs of the same age (54th percentile)

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3 tweeters
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2 Facebook pages

Citations

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41 Dimensions

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85 Mendeley
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Title
Quantifying conformational changes in GPCRs: glimpse of a common functional mechanism
Published in
BMC Bioinformatics, April 2015
DOI 10.1186/s12859-015-0567-3
Pubmed ID
Authors

James AR Dalton, Isaias Lans, Jesús Giraldo

Abstract

G-protein-coupled receptors (GPCRs) are important drug targets and a better understanding of their molecular mechanisms would be desirable. The crystallization rate of GPCRs has accelerated in recent years as techniques have become more sophisticated, particularly with respect to Class A GPCRs interacting with G-proteins. These developments have made it possible for a quantitative analysis of GPCR geometrical features and binding-site conformations, including a statistical comparison between Class A GPCRs in active (agonist-bound) and inactive (antagonist-bound) states. Here we implement algorithms for the analysis of interhelical angles, distances, interactions and binding-site volumes in the transmembrane domains of 25 Class A GPCRs (7 active and 18 inactive). Two interhelical angles change in a statistically significant way between average inactive and active states: TM3-TM6 (by -9°) and TM6-TM7 (by +12°). A third interhelical angle: TM5-TM6 shows a trend, changing by -9°. In the transition from inactive to active states, average van der Waals interactions between TM3 and TM7 significantly increase as the average distance between them decreases by >2 Å. Average H-bonding between TM3 and TM6 decreases but is seemingly compensated by an increase in H-bonding between TM5 and TM6. In five Class A GPCRs, crystallized in both active and inactive states, increased H-bonding of agonists to TM6 and TM7, relative to antagonists, is observed. These protein-agonist interactions likely favour a change in the TM6-TM7 angle, which creates a narrowing in the binding pocket of activated receptors and an average ~200 Å(3) reduction in volume. In terms of similar conformational changes and agonist binding pattern, Class A GPCRs appear to share a common mechanism of activation, which can be exploited in future drug development.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 85 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Italy 1 1%
Brazil 1 1%
Unknown 82 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 18%
Student > Master 15 18%
Student > Bachelor 13 15%
Student > Ph. D. Student 12 14%
Student > Doctoral Student 8 9%
Other 11 13%
Unknown 11 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 24%
Agricultural and Biological Sciences 16 19%
Chemistry 11 13%
Pharmacology, Toxicology and Pharmaceutical Science 9 11%
Computer Science 7 8%
Other 9 11%
Unknown 13 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 15 June 2015.
All research outputs
#8,208,974
of 14,573,111 outputs
Outputs from BMC Bioinformatics
#3,136
of 5,420 outputs
Outputs of similar age
#99,826
of 229,158 outputs
Outputs of similar age from BMC Bioinformatics
#1
of 1 outputs
Altmetric has tracked 14,573,111 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,420 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 39th percentile – i.e., 39% 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 229,158 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them