A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR

Hiroyasu Shimizu, Ying Chun Yu, Koichi Kono, Takahiro Kubota, Masato Yasui, Min Li, Tzyh Chang Hwang, Yoshiro Sohma

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, a member of ABC transporter superfamily, gates following ATP-dependent conformational changes of the nucleotide binding domains (NBD). Reflecting the hundreds of milliseconds duration of the channel open state corresponding to the dimerization of two NBDs, macroscopic WT-CFTR currents usually showed a fast, single exponential relaxation upon removal of cytoplasmic ATP. Mutations of tyrosine1219, a residue critical for ATP binding in second NBD (NBD2), induced a significant slow phase in the current relaxation, suggesting that weakening ATP binding affinity at NBD2 increases the probability of the stable open state. The slow phase was effectively diminished by a higher affinity ATP analogue. These data suggest that a stable binding of ATP to NBD2 is required for normal CFTR gating cycle, andthat the instability of ATP binding frequently halts the gating cycle in the open state presumably through a failure of ATP hydrolysis at NBD2.

Original languageEnglish
Pages (from-to)353-362
Number of pages10
JournalJournal of Physiological Sciences
Volume60
Issue number5
DOIs
Publication statusPublished - 2010 Sep

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Cystic Fibrosis Transmembrane Conductance Regulator
ATP-Binding Cassette Transporters
Nucleotides
Adenosine Triphosphate
Dimerization
Anions
Hydrolysis
Mutation

Keywords

  • ABC transporter
  • Anion channel
  • ATP hydrolysis
  • CFTR
  • Gating

ASJC Scopus subject areas

  • Physiology

Cite this

A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR. / Shimizu, Hiroyasu; Yu, Ying Chun; Kono, Koichi; Kubota, Takahiro; Yasui, Masato; Li, Min; Hwang, Tzyh Chang; Sohma, Yoshiro.

In: Journal of Physiological Sciences, Vol. 60, No. 5, 09.2010, p. 353-362.

Research output: Contribution to journalArticle

Shimizu, Hiroyasu ; Yu, Ying Chun ; Kono, Koichi ; Kubota, Takahiro ; Yasui, Masato ; Li, Min ; Hwang, Tzyh Chang ; Sohma, Yoshiro. / A stable ATP binding to the nucleotide binding domain is important for reliable gating cycle in an ABC transporter CFTR. In: Journal of Physiological Sciences. 2010 ; Vol. 60, No. 5. pp. 353-362.
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AU - Yasui, Masato

AU - Li, Min

AU - Hwang, Tzyh Chang

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