Ionic interaction of the HIV-1 V3 domain with CCR5 and deregulation of T lymphocyte function.
We have reported that the principal neutralizing domain of V3 of the HIV-1 gp120 induces an antigen-specific activation apoptosis of responding effector CD4+ T lymphocytes, a phenomenon inhibited by RANTES, an agonist of CCR5. Here, addressing the question of how a hypervariable region could induce such a selective reaction, we demonstrated that the magnitude of the activation phase was dependent on the number of basic amino acids present in the V3 peptide, an observation confirmed by using V3 peptides with appropriate basic amino acid substitutions. The relative position of the amino acids in the V3 peptide did not affect the biological phenomenon. Using surface plasmon resonance biosensor analysis, we also provided direct evidence of the influence of basic amino acids in the interaction between V3 and the amino terminal domain of CCR5. Sulphation of tyrosines in the CCR5 peptide was essential. Our results confirm gp120 modelling predictions and demonstrate simple molecular ionic interactions as capable of affecting key cell events, the wider biological implications of which need to be further explored.
Baritaki
Stavroula
S
Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.
Zafiropoulos
Alexis
A
Sioumpara
Maria
M
Politis
Manolis
M
Spandidos
Demetrios A
DA
Krambovitis
Elias
E
D000595:Amino Acid Sequence; D017209:Apoptosis; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007477:Ions; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007477:Ions; D010446:Peptide Fragments; D019713:Receptors, CCR5