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Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors.


ABSTRACT: It was posited that functionalities of GPCRs require full-length sequences that are negated by residue deletions. Here we report that significantly truncated nfCCR5QTY and nfCXCR4QTY still bind native ligands. Receptor-ligand interactions were discovered from yeast 2-hybrid screening and confirmed by mating selection. Two nfCCR5QTY (SZ218a, SZ190b) and two nfCXCR4QTY (SZ158a, SZ146a) were expressed in E. coli. Synthesized receptors exhibited ?-helical structures and bound respective ligands with reduced affinities. SZ190b and SZ158a were reconverted into non-QTY forms and expressed in HEK293T cells. Reconverted receptors localized on cell membranes and functioned as negative regulators for ligand-induced signaling when co-expressed with full-length receptors. CCR5-SZ190b individually can perform signaling at a reduced level with higher ligand concentration. Our findings provide insight into essential structural components for CCR5 and CXCR4 functionality, while raising the possibility that non-full-length receptors may be resulted from alternative splicing and that pseudo-genes in genomes may be present and functional in living organisms.

SUBMITTER: Qing R 

PROVIDER: S-EPMC7756140 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Non-full-length Water-Soluble CXCR4<sup>QTY</sup> and CCR5<sup>QTY</sup> Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors.

Qing Rui R   Tao Fei F   Chatterjee Pranam P   Yang Gaojie G   Han Qiuyi Q   Chung Haeyoon H   Ni Jun J   Suter Bernhard P BP   Kubicek Jan J   Maertens Barbara B   Schubert Thomas T   Blackburn Camron C   Zhang Shuguang S  

iScience 20201028 12


It was posited that functionalities of GPCRs require full-length sequences that are negated by residue deletions. Here we report that significantly truncated nfCCR5<sup>QTY</sup> and nfCXCR4<sup>QTY</sup> still bind native ligands. Receptor-ligand interactions were discovered from yeast 2-hybrid screening and confirmed by mating selection. Two nfCCR5<sup>QTY</sup> (SZ218a, SZ190b) and two nfCXCR4<sup>QTY</sup> (SZ158a, SZ146a) were expressed in <i>E. coli</i>. Synthesized receptors exhibited α-h  ...[more]

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