A short amino acid sequence containing tyrosine in the N-terminal region of G protein-coupled receptors is critical for their potential use as co-receptors for human and simian immunodeficiency viruses.
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 co-receptors. 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.
Shimizu
Nobuaki
N
Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Tanaka
Atsushi
A
21st Century COE Program, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.|Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Oue
Atsushi
A
21st Century COE Program, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.|Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Mori
Takahisa
T
21st Century COE Program, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.|Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Apichartpiyakul
Chatchawann
C
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Hoshino
Hiroo
H
21st Century COE Program, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.|Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
D000595:Amino Acid Sequence / Q000235:genetics*; D019943:Amino Acid Substitution; D002460:Cell Line; D015497:HIV-1 / Q000378:metabolism*; D015498:HIV-2 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D054447:Receptors, CCR10 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D013601:T-Lymphocytes; D014443:Tyrosine / Q000737:chemistry*; D000097628:Chemokine Receptor D6
D054447:Receptors, CCR10; D019713:Receptors, CCR5; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D015728:Receptors, HIV; D044067:Receptors, Lipoxin; D011991:Receptors, Virus; D014443:Tyrosine; D000097628:Chemokine Receptor D6; C105101:FPR2 protein, human; C504821:GPR1 protein, human