Article ; Online: Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids.
The Journal of general physiology
2016 Volume 148, Issue 3, Page(s) 227–237
Abstract: ... rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL(-)) with a distinct ... Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids ... to the transmembrane domain (TMD) in each condition. Our results suggest a refined model for phospholipid gating ...
| 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. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Anions/metabolism ; Cell Membrane/metabolism ; Chickens ; Crystallography, X-Ray/methods ; Ion Channel Gating/physiology ; Membrane Proteins/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phospholipids/metabolism ; Potassium/metabolism ; Potassium Channels, Inwardly Rectifying/metabolism ; Protein Domains ; Tryptophan/metabolism | |||||
| Chemical Substances | Anions ; Kir2.2 channel ; Membrane Proteins ; Phosphatidylinositol 4,5-Diphosphate ; Phospholipids ; Potassium Channels, Inwardly Rectifying ; Tryptophan (8DUH1N11BX) ; Potassium (RWP5GA015D) | |||||
| Language | English | |||||
| Publishing date | 2016-08-15 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 3118-5 | |||||
| ISSN | 1540-7748 ; 0022-1295 | |||||
| ISSN (online) | 1540-7748 | |||||
| ISSN | 0022-1295 | |||||
| DOI | 10.1085/jgp.201611616 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Uc I Zs.150: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.