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细胞表面热敏蛋白质组图谱揭示质膜上的扰动和药物靶点
作者:小柯机器人 发布时间:2021/1/5 16:17:49

德国葛兰素史克公司Marcus Bantscheff和H. Christian Eberl团队在最新研究中,揭示了细胞表面热敏蛋白质组图谱揭示了质膜上的扰动和药物靶标。这一研究成果于2021年1月4日发表在《自然-方法学》上。

研究人员利用细胞表面热敏蛋白质组分析,以全面表征配体诱导质膜中蛋白质丰度和热稳定性的变化。研究证明药物结合到细胞外受体和转运蛋白导致刺激依赖性T细胞受体复合物的重塑,并描述了基于竞争的方法来测量G蛋白偶联受体拮抗剂的靶标。响应TGFB受体抑制剂SB431542的处理,质膜蛋白质组重塑导致单羧酸盐转运蛋白MCT1/3部分内化,从而解释了该药物的抗转移作用。

据介绍,许多药物和内源性配体与细胞表面受体结合介导下游信号传导级联的调节,并适应于质膜蛋白质组。由于生化特性和质膜蛋白含量低,对细胞表面动态过程的深入分析具有挑战性。

附:英文原文

Title: Cell surface thermal proteome profiling tracks perturbations and drug targets on the plasma membrane

Author: Mathias Kalxdorf, Ina Gnthner, Isabelle Becher, Nils Kurzawa, Sascha Knecht, Mikhail M. Savitski, H. Christian Eberl, Marcus Bantscheff

Issue&Volume: 2021-01-04

Abstract: Numerous drugs and endogenous ligands bind to cell surface receptors leading to modulation of downstream signaling cascades and frequently to adaptation of the plasma membrane proteome. In-depth analysis of dynamic processes at the cell surface is challenging due to biochemical properties and low abundances of plasma membrane proteins. Here we introduce cell surface thermal proteome profiling for the comprehensive characterization of ligand-induced changes in protein abundances and thermal stabilities at the plasma membrane. We demonstrate drug binding to extracellular receptors and transporters, discover stimulation-dependent remodeling of T cell receptor complexes and describe a competition-based approach to measure target engagement of G-protein-coupled receptor antagonists. Remodeling of the plasma membrane proteome in response to treatment with the TGFB receptor inhibitor SB431542 leads to partial internalization of the monocarboxylate transporters MCT1/3 explaining the antimetastatic effects of the drug. Cell surface thermal proteome profiling allows characterization of ligand-induced changes in protein abundances and thermal stabilities at the plasma membrane.

DOI: 10.1038/s41592-020-01022-1

Source: https://www.nature.com/articles/s41592-020-01022-1

 

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex