3SPC

Inward rectifier potassium channel Kir2.2 in complex with dioctanoylglycerol pyrophosphate (DGPP)

3SPC の概要

• エントリーDOI: 10.2210/pdb3spc/pdb
• 関連するPDBエントリー: 3SPG 3SPH 3SPI 3SPJ
• 分子名称: Inward-rectifier K+ channel Kir2.2, POTASSIUM ION, (2R)-3-{[(R)-hydroxy(phosphonooxy)phosphoryl]oxy}propane-1,2-diyl dioctanoate, ... (4 entities in total)
• 機能のキーワード: pip, membrane protein, lipid, receptor, metal transport
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Membrane; Multi-pass membrane protein (By similarity): D2YW45
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40100.76

構造登録者

Hansen, S.B.,Tao, X.,MacKinnon, R. (登録日: 2011-07-01, 公開日: 2011-08-24, 最終更新日: 2024-11-06)

主引用文献

Hansen, S.B.,Tao, X.,Mackinnon, R.
Structural basis of PIP(2) activation of the classical inward rectifier K(+) channel Kir2.2.
Nature, 477:495-498, 2011

PubMed Abstract: The regulation of ion channel activity by specific lipid molecules is widely recognized as an integral component of electrical signalling in cells. In particular, phosphatidylinositol 4,5-bisphosphate (PIP(2)), a minor yet dynamic phospholipid component of cell membranes, is known to regulate many different ion channels. PIP(2) is the primary agonist for classical inward rectifier (Kir2) channels, through which this lipid can regulate a cell's resting membrane potential. However, the molecular mechanism by which PIP(2) exerts its action is unknown. Here we present the X-ray crystal structure of a Kir2.2 channel in complex with a short-chain (dioctanoyl) derivative of PIP(2). We found that PIP(2) binds at an interface between the transmembrane domain (TMD) and the cytoplasmic domain (CTD). The PIP(2)-binding site consists of a conserved non-specific phospholipid-binding region in the TMD and a specific phosphatidylinositol-binding region in the CTD. On PIP(2) binding, a flexible expansion linker contracts to a compact helical structure, the CTD translates 6 Å and becomes tethered to the TMD and the inner helix gate begins to open. In contrast, the small anionic lipid dioctanoyl glycerol pyrophosphatidic acid (PPA) also binds to the non-specific TMD region, but not to the specific phosphatidylinositol region, and thus fails to engage the CTD or open the channel. Our results show how PIP(2) can control the resting membrane potential through a specific ion-channel-receptor-ligand interaction that brings about a large conformational change, analogous to neurotransmitter activation of ion channels at synapses.

PubMed: 21874019
DOI: 10.1038/nature10370

実験手法

X-RAY DIFFRACTION (2.454 Å)