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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-09, Vol.115 (37), p.E8652-E8659
Main Authors: Zhang, Shuguang, Tao, Fei, Qing, Rui, Tang, Hongzhi, Skuhersky, Michael, Corin, Karolina, Tegler, Lotta, Wassie, Asmamaw, Wassie, Brook, Kwon, Yongwon, Suter, Bernhard, Entzian, Clemens, Schubert, Thomas, Yang, Ge, Labahn, Jörg, Kubicek, Jan, Maertens, Barbara
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
Amino acids
Amino Acids - chemistry
Amino Acids - genetics
Amino Acids - metabolism
Binding
Biological Sciences
CCR5 protein
Chemokine receptors
Chemokines
Coat protein
CXCR4 protein
Detergents
Detergents - chemistry
Domains
G protein-coupled receptors
Glutamine
Glutamine - chemistry
Glutamine - genetics
Glutamine - metabolism
Glycoprotein gp41
Helices
HIV
Hot Temperature
Human immunodeficiency virus
Humans
Hydrophilic surfaces
Hydrophobic and Hydrophilic Interactions
Hydrophobic surfaces
Hydrophobicity
Isoleucine
Leucine
Ligands
Membrane proteins
Membranes
Phenylalanine
PNAS Plus
Protein Binding
Protein Stability
Protein Structure, Secondary
Proteins
Receptor mechanisms
Receptors
Receptors, Chemokine - chemistry
Receptors, Chemokine - genetics
Receptors, Chemokine - metabolism
Solubility
Structure-function relationships
Threonine
Threonine - chemistry
Threonine - genetics
Threonine - metabolism
Tyrosine
Tyrosine - chemistry
Tyrosine - genetics
Tyrosine - metabolism
Valine
Water - chemistry
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Summary: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. CCR5QTY, CXCR4QTY, and CXCR7QTY also bind to HIV coat protein gp41-120. Despite substantial transmembrane domain changes, the detergent-free QTY variants maintain stable structures and retain their ligand-binding activities. We believe the QTY code will be useful for designing water-soluble variants of membrane proteins and other water-insoluble aggregated proteins.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1811031115