Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP-sensitive potassium channels.

Abstract:

:ATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels 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 KATP channels 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 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) 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.

journal_name

Protein Cell

journal_title

Protein & cell

authors

Wu JX,Ding D,Wang M,Kang Y,Zeng X,Chen L

doi

10.1007/s13238-018-0530-y

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

553-567

issue

6

eissn

1674-800X

issn

1674-8018

pii

10.1007/s13238-018-0530-y

journal_volume

9

pub_type

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