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 α-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.

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Truncated Overlooked

Kubicek, Jan, Zhang, Shuguang, Chung, Haeyoon, Tao, Fei, Chatterjee, Pranam, Blackburn, Camron, Ni, Jun, Yang, Gaojie, Schubert, Thomas, Maertens, Barbara,Qing, Rui, Han, Qiuyi, Suter, Bernhard P.,.Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors. (),.

Kubicek, Jan, et al."Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors"

Kubicek, Jan, Zhang, Shuguang, Chung, Haeyoon, Tao, Fei, Chatterjee, Pranam, Blackburn, Camron, Ni, Jun, Yang, Gaojie, Schubert, Thomas, Maertens, Barbara,Qing, Rui, Han, Qiuyi, Suter, Bernhard P.,"Non-full-length Water-Soluble CXCR4QTY and CCR5QTY Chemokine Receptors: Implication for Overlooked Truncated but Functional Membrane Receptors"