XB-ART-41006Science. December 18, 2009; 326 (5960): 1668-74.
Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution.
Inward-rectifier potassium (K+) channels conduct K+ ions most efficiently in one direction, into the cell. Kir2 channels control the resting membrane voltage in many electrically excitable cells, and heritable mutations cause periodic paralysis and cardiac arrhythmia. We present the crystal structure of Kir2.2 from chicken, which, excluding the unstructured amino and carboxyl termini, is 90% identical to human Kir2.2. Crystals containing rubidium (Rb+), strontium (Sr2+), and europium (Eu3+) reveal binding sites along the ion conduction pathway that are both conductive and inhibitory. The sites correlate with extensive electrophysiological data and provide a structural basis for understanding rectification. The channel''s extracellular surface, with large structured turrets and an unusual selectivity filter entryway, might explain the relative insensitivity of eukaryotic inward rectifiers to toxins. These same surface features also suggest a possible approach to the development of inhibitory agents specific to each member of the inward-rectifier K+ channel family.
PubMed ID: 20019282
PMC ID: PMC2819303
Article link: Science.
Grant support: Howard Hughes Medical Institute , R01 GM043949-10 NIGMS NIH HHS , R01 GM043949-11 NIGMS NIH HHS , R01 GM043949-12 NIGMS NIH HHS , R01 GM043949-13 NIGMS NIH HHS , R01 GM043949-14 NIGMS NIH HHS , R01 GM043949-15 NIGMS NIH HHS , R01 GM043949-16 NIGMS NIH HHS , R01 GM043949-17 NIGMS NIH HHS , R01 GM043949-18 NIGMS NIH HHS , R01 GM043949-19 NIGMS NIH HHS , R01 GM043949-20 NIGMS NIH HHS , P30 EB009998 NIBIB NIH HHS , R01 GM043949 NIGMS NIH HHS , HHMI_MACKINNON_R Howard Hughes Medical Institute
Genes referenced: kcnj12