异三聚体G蛋白
G蛋白偶联受体
肽
化学
鸟嘌呤核苷酸交换因子
对接(动物)
生物化学
G蛋白
鸟嘌呤
细胞
信号转导
核苷酸
细胞生物学
生物
基因
医学
护理部
作者
Britta Nubbemeyer,Ajay Abisheck Paul George,Toni Kühl,Anna Pepanian,Maximilian Beck,Riham Ali El maghraby,Maryam A. Shetab Boushehri,Maximilian Muehlhaupt,Eva Marie Pfeil,Suvi Annala,Hermann Ammer,Diana Imhof,Dehua Pei
标识
DOI:10.1021/acschembio.1c00929
摘要
Chemical probes that specifically modulate the activity of heterotrimeric G proteins provide excellent tools for investigating G protein-mediated cell signaling. Herein, we report a family of selective peptidyl Gαi/s modulators derived from peptide library screening and optimization. Conjugation to a cell-penetrating peptide rendered the peptides cell-permeable and biologically active in cell-based assays. The peptides exhibit potent guanine-nucleotide exchange modulator-like activity toward Gαi and Gαs. Molecular docking and dynamic simulations revealed the molecular basis of the protein-ligand interactions and their effects on GDP binding. This study demonstrates the feasibility of developing direct Gαi/s modulators and provides a novel chemical probe for investigating cell signaling through GPCRs/G proteins.
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