Advertisement

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Biological Chemistry

Rescuing A Cystic Fibrosis Protein

Proteomics: Changes in protein interactions restore function of a mutant ion channel involved in the debilitating disease

by Celia Henry Arnaud
December 7, 2015 | A version of this story appeared in Volume 93, Issue 48

The most common cause of cystic fibrosis is a mutation in which a missing phenylalanine leads to an almost complete loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR). This ion channel protein is involved in maintaining salt balance in the lungs and other tissues. CFTR’s function can be partially restored by incubating cells at lower temperatures or inhibiting histone deacetylase enzymes. But how these rescue approaches affect CFTR’s protein interaction network, or interactome, isn’t known. To find out, Sandra Pankow, John R. Yates III, and coworkers at Scripps Research Institute California used immunocoprecipitation and mass spectrometry of cultured human bronchial cells to identify the interactomes for normal and mutated CFTR under normal and rescue conditions (Nature 2015, DOI: 10.1038/nature15729). By comparing how the interaction networks change in response to the rescue strategies, the researchers identified pathways that enable CFTR rescue. Although rescue strategies eliminate most mutant-specific interactions, seven interactions involving protein-degradation machinery persist in both approaches, suggesting that even under rescue conditions mutant CFTR is fated for degradation.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.