A short amino acid sequence containing tyrosine in the N-terminal region of G protein-coupled receptors is critical for their potential use as coreceptors for human and simian immunodeficiency viruses

• Main Authors: Shimizu N., Tanaka A., Oue A., Mori T., Apichartpiyakul C., Hoshino H.
• Format: Article
• Language: English
• Published: 2014
• Online Access: http://www.scopus.com/inward/record.url?eid=2-s2.0-58149388460&partnerID=40&md5=f7d6d191cfd5e5a7f7333292ed0dd1e9; http://cmuir.cmu.ac.th/handle/6653943832/2303
• Institution: Chiang Mai University

Various G protein-coupled receptors (GPCRs) have the potential to work as co-receptors for human and simian immunodeficiency virus (HIV/SIV). HIV/SIV co-receptors have several tyrosines in their extracellular N-terminal region (NTR) as a common feature. However, the domain structure of the NTR that is critical for GPCRs to have co-receptor activity has not been identified. Comparative studies of different HIV/ SIV co-receptors are an effective way to clarify the domain. These studies have been carried out only for the major co-receptors, CCR5 and CXCR4. A chemokine receptor, D6, has been shown to mediate infection of astrocytes with HIV-1. Recently, it was also found that an orphan GPCR, GPR1, and a formyl peptide receptor, FPRL1, work as potent HIV/SIV co-receptors in addition to CCR5 and CXCR4. To elucidate more about the domain of the NTR critical for HIV/SIV co-receptor activity, this study analysed the effects of mutations in the NTR on the co-receptor activity of D6, FPRL1 and GPR1 in addition to CCR5. The results identified a number of tyrosines that are indispensable for the activity of these coreceptors. The number and positions of those tyrosines varied among co-receptors and among HIV-1 strains. Moreover, it was found that a small domain of a few amino acids containing a tyrosine is critical for the co-receptor activity of GPR1. These findings will be useful in elucidating the mechanism that allows GPCRs to have the potential to act as HIV/SIV co-receptors. © 2008 SGM.