5KUM: Crystal Structure Of Inward Rectifier Kir2.2 K62w Mutant In Complex With Pip2

Citation:
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-A 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.
PDB ID: 5KUMDownload
MMDB ID: 142186
PDB Deposition Date: 2016/7/13
Updated in MMDB: 2016/09
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 5KUM: tetrameric; determined by author and by software (PISA)
Molecular Components in 5KUM
Label Count Molecule
Proteins (4 molecules)
4
Atp-sensitive Inward Rectifier Potassium Channel 12(Gene symbol: KCNJ12)
Molecule annotation
Chemicals (24 molecules)
1
4
2
16
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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