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定量检测小鼠巨噬细胞 Toll 样受体和趋化通路的绝对蛋白水平。

Absolute protein quantitation of the mouse macrophage Toll-like receptor and chemotaxis pathways.

机构信息

Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Sci Data. 2022 Aug 12;9(1):491. doi: 10.1038/s41597-022-01612-y.

DOI:10.1038/s41597-022-01612-y
PMID:35961990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9374760/
Abstract

The Toll-like receptor (TLR) and chemotaxis pathways are key components of the innate immune system. Subtle variation in the concentration, timing, and molecular structure of the ligands are known to affect downstream signaling and the resulting immune response. Computational modeling and simulation at the molecular interaction level can be used to study complex biological pathways, but such simulations require protein concentration values as model parameters. Here we report the development and application of targeted mass spectrometry assays to measure the absolute abundance of proteins of the mouse macrophage Toll-like receptor 4 (TLR4) and chemotaxis pathways. Two peptides per protein were quantified, if possible. The protein abundance values ranged from 1,332 to 227,000,000 copies per cell. They moderately correlated with transcript abundance values from a previously published mouse macrophage RNA-seq dataset, and these two datasets were combined to make proteome-wide abundance estimates. The datasets produced during this investigation can be used for pathway modeling and simulation, as well as for other studies of the TLR and chemotaxis pathways.

摘要

Toll 样受体 (TLR) 和趋化作用途径是先天免疫系统的关键组成部分。已知配体的浓度、时间和分子结构的细微变化会影响下游信号转导和产生的免疫反应。在分子相互作用水平上进行计算建模和模拟可以用于研究复杂的生物学途径,但这种模拟需要蛋白质浓度值作为模型参数。在这里,我们报告了靶向质谱测定法的开发和应用,以测量小鼠巨噬细胞 Toll 样受体 4 (TLR4) 和趋化作用途径的蛋白质的绝对丰度。如果可能的话,每个蛋白质测量两个肽段。蛋白质丰度值范围为每个细胞 1,332 到 227,000,000 个拷贝。它们与之前发表的小鼠巨噬细胞 RNA-seq 数据集的转录本丰度值中度相关,这两个数据集被合并以进行全蛋白质组丰度估计。在此研究中产生的数据集可用于途径建模和模拟,以及用于 TLR 和趋化作用途径的其他研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/3b70ac8fbbf7/41597_2022_1612_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/ed1ce1c8c2e9/41597_2022_1612_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/97a45f092e39/41597_2022_1612_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/e8572ac27eb0/41597_2022_1612_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/840d03c91c44/41597_2022_1612_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/5a6f5c5f4837/41597_2022_1612_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/3b70ac8fbbf7/41597_2022_1612_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/ed1ce1c8c2e9/41597_2022_1612_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/97a45f092e39/41597_2022_1612_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/e8572ac27eb0/41597_2022_1612_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/840d03c91c44/41597_2022_1612_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/5a6f5c5f4837/41597_2022_1612_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b2e/9374760/3b70ac8fbbf7/41597_2022_1612_Fig6_HTML.jpg

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