5KUK

Crystal Structure of Inward Rectifier Kir2.2 K62W Mutant

Summary for 5KUK

• Entry DOI: 10.2210/pdb5kuk/pdb
• Related: 5KUM
• Descriptor: ATP-sensitive inward rectifier potassium channel 12, POTASSIUM ION, DECYL-BETA-D-MALTOPYRANOSIDE, ... (4 entities in total)
• Functional Keywords: metal transport kir 2.2 k62w mutant structure, metal transport
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 1
• Total formula weight: 40253.20

Authors

Lee, S.-J.,Ren, F.,Heyman, S.,Yuan, P.,Nichols, C.G. (deposition date: 2016-07-13, release date: 2016-08-10, Last modification date: 2024-10-09)

Primary citation

Lee, S.J.,Ren, F.,Zangerl-Plessl, E.M.,Heyman, S.,Stary-Weinzinger, A.,Yuan, P.,Nichols, C.G.
Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids.
J.Gen.Physiol., 148:227-237, 2016

PubMed 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.

PubMed: 27527100
DOI: 10.1085/jgp.201611616

Experimental method

X-RAY DIFFRACTION (2 Å)