More abundant than all other anions in the body, chloride is “the counterion of life,” says Sheel C. Dodani of the University of Texas at Dallas. It plays an important role in muscle contractions and neurotransmission, among other functions. Now, in a discovery that may lead to better tools for the study of chloride in living cells, researchers identified the first natural protein that fluoresces upon binding chloride. (Biochemistry; 2018. DOI: 10.1021/acsbiochem.8b00928).
Beyond basic science, tracking chloride’s concentrations in the body could help researchers understand diseases that are related to defects in chloride transport, such as epilepsy and cystic fibrosis. Scientists have developed a number of small molecules and engineered fluorescent proteins that sense chloride. However, these tools each have drawbacks, such as a limited pH range, which prevents their use in living cells.
Seeking a better sensor, Dodani’s team used an engineered protein that fluoresces yellow in the presence of chloride as a model. They searched the global protein sequence database for similar natural proteins and found a closely related homolog of unknown function in the jellyfish Phialidium sp. After producing the protein using bacteria, the team found that, it indeed glowed in response to chloride. While still pH dependent, the jellyfish protein could be engineered to shift its pH range and to boost its chloride sensitivity, Dodani says.