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EMBO J. 2003 Aug 1;22(15):3833-43.

N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits.

Author information

1
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA. kwc8@po.cwru.edu

Abstract

The sulfonylurea receptor (SUR), an ATP-binding cassette (ABC) protein, assembles with a potassium channel subunit (Kir6) to form the ATP-sensitive potassium channel (K(ATP)) complex. Although SUR is an important regulator of Kir6, the specific SUR domain that associates with Kir6 is still unknown. All functional ABC proteins contain two transmembrane domains but some, including SUR and MRP1 (multidrug resistance protein 1), contain an extra N-terminal transmembrane domain called TMD0. The functions of any TMD0s are largely unclear. Using Xenopus oocytes to coexpress truncated SUR constructs with Kir6, we demonstrated by immunoprecipitation, single-oocyte chemiluminescence and electrophysiological measurements that the TMD0 of SUR1 strongly associated with Kir6.2 and modulated its trafficking and gating. Two TMD0 mutations, A116P and V187D, previously correlated with persistent hyperinsulinemic hypoglycemia of infancy, were found to disrupt the association between TMD0 and Kir6.2. These results underscore the importance of TMD0 in K(ATP) channel function, explaining how specific mutations within this domain result in disease, and suggest how an ABC protein has evolved to regulate a potassium channel.

PMID:
12881418
PMCID:
PMC169049
DOI:
10.1093/emboj/cdg376
[Indexed for MEDLINE]
Free PMC Article

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