Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels
Copyright policy )Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels
ABSTRACTATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATPchannels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic KATPchannels solved by cryo-electron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 N-terminus participates the coupling between the peripheral SUR1 subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit.
- Peking University China (People's Republic of)
- PEKING UNIVERSITY China (People's Republic of)
- INSTITUTE OF MOLECULAR MEDICINE
- Peking University China (People's Republic of)
- Tsinghua University China (People's Republic of)
Models, Molecular, sulfonylurea, Spodoptera, Ligands, Sulfonylurea Receptors, Mice, Adenosine Triphosphate, Sf9 Cells, Animals, Amino Acid Sequence, Potassium Channels, Inwardly Rectifying, Protein Structure, Quaternary, Pancreas, Binding Sites, SUR, diabetes, QH573-671, Mesocricetus, Nucleotides, Cryoelectron Microscopy, QP501-801, KATP, Animal biochemistry, Protein Subunits, glibenclamide, ABC transporter, Protein Multimerization, Cytology, Research Article, Protein Binding
Models, Molecular, sulfonylurea, Spodoptera, Ligands, Sulfonylurea Receptors, Mice, Adenosine Triphosphate, Sf9 Cells, Animals, Amino Acid Sequence, Potassium Channels, Inwardly Rectifying, Protein Structure, Quaternary, Pancreas, Binding Sites, SUR, diabetes, QH573-671, Mesocricetus, Nucleotides, Cryoelectron Microscopy, QP501-801, KATP, Animal biochemistry, Protein Subunits, glibenclamide, ABC transporter, Protein Multimerization, Cytology, Research Article, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).96 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!