ADVERTISEMENT
2 /3 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.

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

Inorganic Chemistry

Making chimeric versions of chemokine receptors

Swapping hydrophobic amino acids for hydrophilic ones allows researchers to make water-soluble, detergent-free versions of transmembrane proteins

by Celia Henry Arnaud
December 1, 2019 | APPEARED IN VOLUME 97, ISSUE 47

09747-scicon7-loops.jpg
Credit: Proc. Natl. Acad. Sci. USA
A chimeric chemokine receptor (right) is made by combining the extracellular loops of one chemokine receptor (left) and the transmembrane domain of another (center.)

Chemokine receptors are a family of structurally similar transmembrane proteins, each of which is selective for a specific ligand. Because the proteins need detergents to stabilize them, their binding properties are hard to study. Last year, Shuguang Zhang of the Massachusetts Institute of Technology and coworkers reported a QTY code that eliminates the need for detergents by replacing hydrophobic amino acids with structurally similar hydrophilic ones. The proteins become water-soluble even while maintaining their native structure, which simplifies analysis. Zhang, postdoc Rui Qing, and coworkers have now used the code to make and study the binding properties of five chemokine receptor QTY variants and chimeric chemokine receptors (Proc. Natl. Acad. Sci. U.S.A. 2019, DOI: 10.1073/pnas.1909026116). The researchers show that QTY chemokine receptors produced in Escherichia coli bind their native ligands with similar affinities as the native receptors. By combining a QTY version of the transmembrane portion of one chemokine receptor with the extracellular loops of another, the researchers made chimeric receptors. They determined that these chimeric receptors are better able to bind the ligand that goes with the extracellular loops than with the transmembrane domain. “We can now use one transmembrane domain receptor scaffold and append the other 20 kinds of chemokine receptor extracellular domains in order to systematically study how these receptors finely distinguish their ligands,” Zhang says. He adds that that the chimeric receptors may be useful as sensors with tunable ligand affinity.

Advertisement
X

Article:

This article has been sent to the following recipient:

Leave A Comment

*Required to comment