New understanding of gating mechanism of CFTR chloride channel

April 26, 2010

New research advances our understanding of the gating mechanism of the CFTR, the chloride channel mutated in cystic fibrosis patients. The study by Tzyh-Chang Hwang and colleagues (University of Missouri), and accompanying Commentary by László Csanády (Semmelweis University) appear in the May issue of the Journal of General Physiology.

CFTR is a member of the superfamily of ABC proteins found in all organisms, from bacteria to human. The 48 human ABC proteins mostly mediate transmembrane export of substrates at the expense of ATP hydrolysis. They are involved in a wide variety of physiological processes, ranging from insulin secretion to drug detoxification.

Like other ABC proteins, CFTR encompasses two nucleotide binding domains (NBD1 and NDB2), which form a dimer. It is generally accepted that CFTR's opening-closing cycles, each completed within one second, are driven by rapid ATP binding and hydrolysis events in NBD2. Now, using real-time recording, Hwang and colleagues tackle the fundamental question of whether the NBD dimer fully dissociates in each gating cycle, and they provide strong evidence that it does not. The authors propose a gating model for CFTR with a "partial" separation of the NBD dimer, with two distinct cycles.

Explore further: Technology reveals 'lock and key' proteins behind diseases

More information:
Tsai, M.-F., M. Li, and T.-C. Hwang. 2010. J. Gen. Physiol. doi:10.1085/jgp.201010399
Csanády, L. 2010.J. Gen. Physiol. doi:10.1085/jgp.201010443

Related Stories

Experiments point to new treatments for PKD

April 2, 2008

A family of small molecules called CFTR inhibitors show promising effects in slowing the progression of polycystic kidney disease (PKD), the most common genetic disease of the kidneys, according to preliminary research reported ...

Recommended for you

New method developed for producing some metals

August 25, 2016

The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and ...

Force triggers gene expression by stretching chromatin

August 26, 2016

How genes in our DNA are expressed into traits within a cell is a complicated mystery with many players, the main suspects being chemical. However, a new study by University of Illinois researchers and collaborators in China ...

New electrical energy storage material shows its power

August 24, 2016

A powerful new material developed by Northwestern University chemist William Dichtel and his research team could one day speed up the charging process of electric cars and help increase their driving range.

Bio-inspired tire design: Where the rubber meets the road

August 24, 2016

The fascination with the ability of geckos to scamper up smooth walls and hang upside down from improbable surfaces has entranced scientists at least as far back as Aristotle, who noted the reptile's remarkable feats in his ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.