QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities.

ABSTRACT: Structure and function studies of membrane proteins, particularly G protein-coupled receptors and multipass transmembrane proteins, require detergents. We have devised a simple tool, the QTY code (glutamine, threonine, and tyrosine), for designing hydrophobic domains to become water soluble without detergents. Here we report using the QTY code to systematically replace the hydrophobic amino acids leucine, valine, isoleucine, and phenylalanine in the seven transmembrane α-helices of CCR5, CXCR4, CCR10, and CXCR7. We show that QTY code-designed chemokine receptor variants retain their thermostabilities, α-helical structures, and ligand-binding activities in buffer and 50% human serum. CCR5^QTY, CXCR4^QTY, and CXCR7^QTY also bind to HIV coat protein gp41-120. Des

SUBMITTER: Zhang S 

PROVIDER: S-EPMC6140526 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature