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Finding a Needle in a Haystack: The Role of Electrostatics in Target Lipid Recognition by PH Domains

Overview of attention for article published in PLoS Computational Biology, July 2012
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35 Dimensions

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51 Mendeley
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Title
Finding a Needle in a Haystack: The Role of Electrostatics in Target Lipid Recognition by PH Domains
Published in
PLoS Computational Biology, July 2012
DOI 10.1371/journal.pcbi.1002617
Pubmed ID
Authors

Craig N. Lumb, Mark S. P. Sansom

Abstract

Interactions between protein domains and lipid molecules play key roles in controlling cell membrane signalling and trafficking. The pleckstrin homology (PH) domain is one of the most widespread, binding specifically to phosphatidylinositol phosphates (PIPs) in cell membranes. PH domains must locate specific PIPs in the presence of a background of approximately 20% anionic lipids within the cytoplasmic leaflet of the plasma membrane. We investigate the mechanism of such recognition via a multiscale procedure combining Brownian dynamics (BD) and molecular dynamics (MD) simulations of the GRP1 PH domain interacting with phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P₃). The interaction of GRP1-PH with PI(3,4,5)P₃ in a zwitterionic bilayer is compared with the interaction in bilayers containing different levels of anionic 'decoy' lipids. BD simulations reveal both translational and orientational electrostatic steering of the PH domain towards the PI(3,4,5)P₃-containing anionic bilayer surface. There is a payoff between non-PIP anionic lipids attracting the PH domain to the bilayer surface in a favourable orientation and their role as 'decoys', disrupting the interaction of GRP1-PH with the PI(3,4,5)P₃ molecule. Significantly, approximately 20% anionic lipid in the cytoplasmic leaflet of the bilayer is nearly optimal to both enhance orientational steering and to localise GRP1-PH proximal to the surface of the membrane without sacrificing its ability to locate PI(3,4,5)P₃ within the bilayer plane. Subsequent MD simulations reveal binding to PI(3,4,5)P₃, forming protein-phosphate contacts comparable to those in X-ray structures. These studies demonstrate a computational framework which addresses lipid recognition within a cell membrane environment, offering a link between structural and cell biological characterisation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 4%
Japan 1 2%
Czechia 1 2%
Austria 1 2%
Unknown 46 90%

Demographic breakdown

Readers by professional status Count As %
Researcher 22 43%
Student > Ph. D. Student 15 29%
Student > Bachelor 3 6%
Student > Master 3 6%
Professor 2 4%
Other 4 8%
Unknown 2 4%
Readers by discipline Count As %
Agricultural and Biological Sciences 20 39%
Biochemistry, Genetics and Molecular Biology 14 27%
Chemistry 4 8%
Physics and Astronomy 3 6%
Neuroscience 1 2%
Other 3 6%
Unknown 6 12%
Attention Score in Context

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 03 August 2012.
All research outputs
#15,740,207
of 25,374,917 outputs
Outputs from PLoS Computational Biology
#6,754
of 8,960 outputs
Outputs of similar age
#107,267
of 178,784 outputs
Outputs of similar age from PLoS Computational Biology
#74
of 110 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,960 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.4. This one is in the 22nd percentile – i.e., 22% 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 178,784 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 110 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.