Evidence map›Paper›PMID 27527100›Full record

ArticleThe Journal of general physiology2016

Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids.

Sun-Joo Lee, Feifei Ren, Eva-Maria Zangerl-Plessl, Sarah Heyman, Anna Stary-Weinzinger, Peng Yuan, Colin G Nichols

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

55 citing papers in PubMed, 70 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Extracellular Kir2.1Circulation research · 2024
    Article
  6. Bidirectional Allosteric Coupling between PIPInternational journal of molecular sciences · 2024
    Article
  7. Frontiers in physiology · 2024
    Article
  8. Article
  9. Extracellular cysteine disulfide bond break at Cys122 disrupts PIPbioRxiv : the preprint server for biology · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Oxidation Driven Reversal of PIPFunction (Oxford, England) · 2023
    Article
  14. CL-705G: a novel chemical Kir6.2-specific KFrontiers in pharmacology · 2023
    Article
  15. Cholesterol and PIPAdvances in experimental medicine and biology · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

7 authors at 2 institutions in 2 countries.

Sun-Joo LeeDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110.
Feifei RenDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110.
Eva-Maria Zangerl-PlesslDepartment of Pharmacology and Toxicology, University of Vienna, A-1090 Vienna, Austria.
Sarah HeymanDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110.
Anna Stary-WeinzingerDepartment of Pharmacology and Toxicology, University of Vienna, A-1090 Vienna, Austria.ORCID 0000-0002-9202-0484
Peng YuanDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110.
Colin G NicholsDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO 63110 cnichols@wustl.edu.
Washington University in St. Louis · USUniversity of Vienna · AT

Funding

Rectification &Block of Ion Channel CurrentsR01HL054171 · NHLBI · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 1995 to 2017
$4.5M
Austrian Science Fund FWF I 2101Austrian Science Fund FWF W 1232NHLBI NIH HHS R01 HL054171
6 · The paper itself

Abstract

Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP2) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL(-)) with a distinct second site is required for high PIP2 sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP2 sensitivity, even in the absence of PL(-) Furthermore, high-resolution x-ray crystal structures of Kir2.2[K62W], with or without added PIP2 (2.8- and 2.0-Å resolution, respectively), reveal tight tethering of the C-terminal domain (CTD) to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating in which PL(-) binding at the second site pulls the CTD toward the membrane, inducing the formation of the high-affinity primary PIP2 site and explaining the positive allostery between PL(-) binding and PIP2 sensitivity.

Indexed as

AnimalsAnionsCell MembraneChickensCrystallography, X-RayIon Channel GatingMembrane ProteinsPhosphatidylinositol 4,5-DiphosphatePhospholipidsPotassiumPotassium Channels, Inwardly RectifyingProtein DomainsTryptophanAnionsKir2.2 channelMembrane ProteinsPhosphatidylinositol 4,5-DiphosphatePhospholipidsPotassiumPotassium Channels, Inwardly RectifyingTryptophan

Identifiers

PMID27527100
PMCPMC5004336
OpenAlexW2507433039

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.