Molecular mechanisms of interaction of polycationic peptides with serpentine type receptors and heterotrimeric G-proteins in rat tissues
Tóm tắt
The key step in the hormonal signal transduction into cell is interaction of receptors with heterotrimeric G-proteins. We and other authors have shown that G-proteins may be activated as a result of their direct interaction with polycationic peptides. The goal of this work was to study molecular mechanisms of effect of hydrophobic peptide I, C-εAhx-WKK(C10)-KKK(C10)-KKKK(C10)-YKK(C10)-KK, and branched peptide II, [(GRGDSGRKKRRQRRRPPQ)2-K-εAhx-C]2 including the 48–60 fragment of the HIV-1 TAT-protein, on receptor and G-protein. These two peptides (10−6−10−4 M) produced a dose-dependent simulation of the GTP-binding activity of G-proteins in plasma membrane fractions of the brain striatum and cardiac muscle in rats. The effect of peptide I was more pronounced and decreased to a considerable degree in the presence of the C-terminal 385–394 peptide of the G-protein αs-subunit that selectively disrupts interaction of receptors with Gs-protein. Peptide I reduced markedly affinity of serotonin (agonist) to the serotonin striatum receptors, whereas peptide II inhibited to the significant extent the binding of dihydroalprenolol (antagonist) to β-adrenergic receptors in cardiac muscle. Peptide I, unlike peptide II, decreased essentially the high affinity binding of β-agonist isoproterenol. The obtained data indicate the ability of polycationic peptides to activate G1-proteins, to disturb their coupling with receptor, and to affect binding properties of the receptor. There are differences in molecular mechanisms of action of peptides with different structures on G-proteins and receptors.
Tài liệu tham khảo
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