Evidence map›Paper›PMID 23564459›Full record

ArticleThe Journal of biological chemistry2013

Energetics and location of phosphoinositide binding in human Kir2.1 channels.

Nazzareno D'Avanzo, Sun-Joo Lee, Wayland W L Cheng, Colin G Nichols

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. PIPFunction (Oxford, England) · 2021
    Article
  10. PIPProceedings of the National Academy of Sciences of the United States of America · 2020
    Review
  11. Article
  12. A network of phosphatidylinositol 4,5-bisphosphate binding sites regulates gating of the CaProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  13. Article
  14. Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIPProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Nazzareno D'AvanzoDepartment of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, Saint Louis, Missouri 63110. Electronic address: nazzareno.d.avanzo@umontreal.ca.
Sun-Joo LeeDepartment of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, Saint Louis, Missouri 63110.
Wayland W L ChengDepartment of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, Saint Louis, Missouri 63110.
Colin G NicholsDepartment of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, Saint Louis, Missouri 63110. Electronic address: cnichols@wustl.edu.
Washington University in St. Louis · US

Funding

Rectification &Block of Ion Channel CurrentsR01HL054171 · NHLBI · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 1995 to 2017
$4.5M
LIPID REGULATION OF PURIFIED EUKARYOTIC POTASSIUM CHANNELSK99HL112300 · NHLBI · WASHINGTON UNIVERSITY · PI D'AVANZO, NAZZARENO · 2012 to 2012
$47k
NHLBI NIH HHS HL54171NHLBI NIH HHS K99 HL112300NHLBI NIH HHS K99 HL112300-01NHLBI NIH HHS R01 HL054171
6 · The paper itself

Abstract

Kir2.1 channels are uniquely activated by phosphoinositide 4,5-bisphosphate (PI(4,5)P2) and can be inhibited by other phosphoinositides (PIPs). Using biochemical and computational approaches, we assess PIP-channel interactions and distinguish residues that are energetically critical for binding from those that alter PIP sensitivity by shifting the open-closed equilibrium. Intriguingly, binding of each PIP is disrupted by a different subset of mutations. In silico ligand docking indicates that PIPs bind to two sites. The second minor site may correspond to the secondary anionic phospholipid site required for channel activation. However, 96-99% of PIP binding localizes to the first cluster, which corresponds to the general PI(4,5)P2 binding location in recent Kir crystal structures. PIPs can encompass multiple orientations; each di- and triphosphorylated species binds with comparable energies and is favored over monophosphorylated PIPs. The data suggest that selective activation by PI(4,5)P2 involves orientational specificity and that other PIPs inhibit this activation through direct competition.

Indexed as

Molecular Docking SimulationBinding SitesCrystallography, X-RayHumansPhosphatidylinositol 4,5-DiphosphatePotassium Channels, Inwardly RectifyingProtein BindingKCNJ2 protein, humanPhosphatidylinositol 4,5-DiphosphatePotassium Channels, Inwardly RectifyingLipidsMolecular DockingMolecular ModelingPhosphatidylinositol PhosphatasePotassium Channels

Identifiers

PMID23564459
PMCPMC3675606
OpenAlexW1967995354

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.