Journal
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
Volume 364, Issue 1514, Pages 247-255Publisher
ROYAL SOC
DOI: 10.1098/rstb.2008.0191
Keywords
CFTR; ion channel; ATP-binding cassette transporter; ATP binding and hydrolysis; gating
Categories
Funding
- Medical Research Council UK [G0501200]
- Wellcome Trust [081298/Z/06/Z]
- NIH USA [DK51767]
- Wellcome Trust [081298/Z/06/Z] Funding Source: Wellcome Trust
- MRC [G0501200] Funding Source: UKRI
- Medical Research Council [G0501200] Funding Source: researchfish
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Proteins belonging to the ATP-binding cassette superfamily couple ATP binding and hydrolysis at conserved nucleotide-binding domains (NBDs) to diverse cellular functions. Most superfamily members are transporters, while cystic fibrosis transmembrane conductance regulator (CFTR), alone, is an ion channel. Despite this functional difference, recent results have suggested that CFTR shares a common molecular mechanism with other members. ATP binds to partial binding sites on the surface of the two NBDs, which then associate to form a NBD dimer, with complete composite catalytic sites now buried at the interface. ATP hydrolysis and gamma-phosphate dissociation, with the loss of molecular contacts linking the two sides of the composite site, trigger dimer dissociation. The conformational signals generated by NBD dimer formation and dissociation are transmitted to the transmembrane domains where, in transporters, they drive the cycle of conformational changes that translocate the substrate across the membrane; in CFTR, they result in opening and closing (gating) of the ion-permeation pathway.
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