Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution.

TitleCrystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution.
Publication TypeJournal Article
Year of Publication2009
AuthorsTao, X, Avalos, JL, Chen, J, MacKinnon, R
JournalScience
Volume326
Issue5960
Pagination1668-74
Date Published2009 Dec 18
ISSN1095-9203
KeywordsAmino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Chickens, Cloning, Molecular, Crystallography, X-Ray, Europium, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Molecular Sequence Data, Oocytes, Patch-Clamp Techniques, Potassium, Potassium Channel Blockers, Potassium Channels, Inwardly Rectifying, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, Rubidium, Sequence Alignment, Strontium, Xenopus laevis
Abstract

<p>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.</p>

DOI10.1126/science.1180310
Alternate JournalScience
PubMed ID20019282
PubMed Central IDPMC2819303
Grant ListR01 GM043949-12 / GM / NIGMS NIH HHS / United States
R01 GM043949-19 / GM / NIGMS NIH HHS / United States
R01 GM043949 / GM / NIGMS NIH HHS / United States
R01 GM043949-15 / GM / NIGMS NIH HHS / United States
R01 GM043949-13 / GM / NIGMS NIH HHS / United States
R01 GM043949-16 / GM / NIGMS NIH HHS / United States
R01 GM043949-11 / GM / NIGMS NIH HHS / United States
R01 GM043949-14 / GM / NIGMS NIH HHS / United States
R01 GM043949-10 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P30 EB009998 / EB / NIBIB NIH HHS / United States
R01 GM043949-17 / GM / NIGMS NIH HHS / United States
R01 GM043949-20 / GM / NIGMS NIH HHS / United States
R01 GM043949-18 / GM / NIGMS NIH HHS / United States