3spc

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

spinqualitylabelsall models 3spc, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3spc is a 1 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.454Å Ligands: K, P8P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KCJ12_CHICK Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable cells. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. The inward rectification is probably due to the blockage of outward current by cytoplasmic polyamines and/or magnesium ions. Publication Abstract from PubMed 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 A 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. Structural basis of PIP(2) activation of the classical inward rectifier K(+) channel Kir2.2.,Hansen SB, Tao X, Mackinnon R Nature. 2011 Aug 28. doi: 10.1038/nature10370. PMID:21874019 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium channel 3D structures

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