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Structural biology of presenilin 1 complexes

Overview of attention for article published in Molecular Neurodegeneration, December 2014
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2 tweeters
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Citations

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34 Dimensions

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102 Mendeley
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1 CiteULike
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Title
Structural biology of presenilin 1 complexes
Published in
Molecular Neurodegeneration, December 2014
DOI 10.1186/1750-1326-9-59
Pubmed ID
Authors

Yi Li, Christopher Bohm, Roger Dodd, Fusheng Chen, Seema Qamar, Gerold Schmitt-Ulms, Paul E Fraser, Peter H St George-Hyslop

Abstract

The presenilin genes were first identified as the site of missense mutations causing early onset autosomal dominant familial Alzheimer's disease. Subsequent work has shown that the presenilin proteins are the catalytic subunits of a hetero-tetrameric complex containing APH1, nicastrin and PEN-2. This complex (variously termed presenilin complex or gamma-secretase complex) performs an unusual type of proteolysis in which the transmembrane domains of Type I proteins are cleaved within the hydrophobic compartment of the membrane. This review describes some of the molecular and structural biology of this unusual enzyme complex. The presenilin complex is a bilobed structure. The head domain contains the ectodomain of nicastrin. The base domain contains a central cavity with a lateral cleft that likely provides the route for access of the substrate to the catalytic cavity within the centre of the base domain. There are reciprocal allosteric interactions between various sites in the complex that affect its function. For instance, binding of Compound E, a peptidomimetic inhibitor to the PS1 N-terminus, induces significant conformational changes that reduces substrate binding at the initial substrate docking site, and thus inhibits substrate cleavage. However, there is a reciprocal allosteric interaction between these sites such that prior binding of the substrate to the initial docking site paradoxically increases the binding of the Compound E peptidomimetic inhibitor. Such reciprocal interactions are likely to form the basis of a gating mechanism that underlies access of substrate to the catalytic site. An increasingly detailed understanding of the structural biology of the presenilin complex is an essential step towards rational design of substrate- and/or cleavage site-specific modulators of presenilin complex function.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 102 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
United States 1 <1%
Germany 1 <1%
Brazil 1 <1%
Unknown 98 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 23%
Researcher 18 18%
Student > Bachelor 17 17%
Student > Master 11 11%
Student > Doctoral Student 6 6%
Other 13 13%
Unknown 14 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 22 22%
Biochemistry, Genetics and Molecular Biology 18 18%
Neuroscience 15 15%
Medicine and Dentistry 10 10%
Chemistry 7 7%
Other 11 11%
Unknown 19 19%

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 05 January 2015.
All research outputs
#12,361,236
of 18,804,592 outputs
Outputs from Molecular Neurodegeneration
#602
of 730 outputs
Outputs of similar age
#182,390
of 324,566 outputs
Outputs of similar age from Molecular Neurodegeneration
#37
of 46 outputs
Altmetric has tracked 18,804,592 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 730 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.9. This one is in the 11th percentile – i.e., 11% 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 324,566 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.