کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1927982 1536771 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biochemical characterization of a heterotrimeric Gi-protein activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Biochemical characterization of a heterotrimeric Gi-protein activator peptide designed from the junction between the intracellular third loop and sixth transmembrane helix in the m4 muscarinic acetylcholine receptor
چکیده انگلیسی


• The peptide m4i3c(14)Gly displays GEF activity toward Gαi1.
• m4i3c(14)Gly forms a stable complex with the nucleotide-free Gαi1.
• The m4i3c(14)Gly−Gαi1 complex aggregated to form larger particles.
• The VTIF motif in m4i3c(14)Gly plays a key role in binding to Gαi1.

Muscarinic acetylcholine receptors (mAChRs) are G-protein coupled receptors (GPCRs) that are activated by acetylcholine released from parasympathetic nerves. The mAChR family comprises 5 subtypes, m1–m5, each of which has a different coupling selectivity for heterotrimeric GTP-binding proteins (G-proteins). m4 mAChR specifically activates the Gi/o family by enhancing the guanine nucleotide exchange factor (GEF) reaction with the Gα subunit through an interaction that occurs via intracellular segments. Here, we report that the m4 mAChR mimetic peptide m4i3c(14)Gly, comprising 14 residues in the junction between the intracellular third loop (i3c) and transmembrane helix VI (TM-VI) extended with a C-terminal glycine residue, presents GEF activity toward the Gi1 α subunit (Gαi1). The m4i3c(14)Gly forms a stable complex with guanine nucleotide-free Gαi1 via three residues in the VTI(L/F) motif, which is conserved within the m2/4 mAChRs. These results suggest that this m4 mAChR mimetic peptide, which comprises the amino acid of the mAChR intracellular segments, is a useful tool for understanding the interaction between GPCRs and G-proteins.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issues 1–2, 17–24 July 2015, Pages 64–69
نویسندگان
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