Work

The Nucleotide-Binding Sites of SUR1: A Mechanistic Model

Year: 2015

Type: review

Abstract: ATP-sensitive potassium (KATP) channels comprise four pore-forming Kir6.2 subunits and four modulatory sulfonylurea receptor (SUR) subunits. The latter belong to the ATP-binding cassette family of transporters. KATP channels are inhibited by ATP (or ADP) binding to Kir6.2 and activated by Mg-nucleotide interactions with SUR. This dual regulation enables the KATP channel to couple the metabolic state of a cell to its electrical excitability and is crucial for the KATP channel's role in regulating insulin secretion, cardiac and neuronal excitability, and vascular tone. Here, we review the regulation of the KATP channel by adenine nucleotides and present an equilibrium allosteric model for nucleotide activation and inhibition. The model can account for many experimental observations in the literature and provides testable predictions for future experiments.

Source: Biophysical Journal

DOI: 10.1016/j.bpj.2015.10.026

Authors: Natascia Vedovato, Frances M. Ashcroft, Michael C. Puljung

Institution: University of Oxford

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $1,732