New understanding of gating mechanism of CFTR chloride channel

Apr 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: Chemical biologists find new halogenation enzyme

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

add to favorites email to friend print save as pdf

Related Stories

Experiments point to new treatments for PKD

Apr 02, 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

Chemical biologists find new halogenation enzyme

Sep 15, 2014

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

Sep 15, 2014

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

Sep 15, 2014

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

Sep 15, 2014

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

User comments : 0