美国密歇根大学Wenjing Wang和Peng Li团队近期取得重要工作进展，他们研究开发了一种多肽功能化学遗传控制的通用方法。这一研究成果2022年12月8日在线发表于《自然—方法学》杂志上。
据介绍，天然或工程肽具有重要的生物学功能。实现短肽化学依赖性激活的一般方法对于细胞过程的空间和时间控制将非常有价值。
研究人员提出了一对化学激活的蛋白质结构域（CAP），用于控制肽的N端和C端部分的可及性。CAP是通过FK506结合蛋白的定向演化开发的。通过将肽与一个或两个CAP融合，肽的功能被阻断，直到小分子将其从FK506结合蛋白配体结合位点置换，功能才会被激活。CAP通常适用于一系列短肽，包括蛋白酶切割位点、二聚化诱导七肽、核定位信号肽和阿片肽，其化学依赖性高达156倍。
研究人员表明，CAP系统可用于细胞培养和活体动物的多器官。
附：英文原文
Title: A general method for chemogenetic control of peptide function
Author: Shen, Jiaqi, Geng, Lequn, Li, Xingyu, Emery, Catherine, Kroning, Kayla, Shingles, Gwendolyn, Lee, Kerry, Heyden, Matthias, Li, Peng, Wang, Wenjing
Issue&Volume: 2022-12-08
Abstract: Natural or engineered peptides serve important biological functions. A general approach to achieve chemical-dependent activation of short peptides will be valuable for spatial and temporal control of cellular processes. Here we present a pair of chemically activated protein domains (CAPs) for controlling the accessibility of both the N- and C-terminal portion of a peptide. CAPs were developed through directed evolution of an FK506-binding protein. By fusing a peptide to one or both CAPs, the function of the peptide is blocked until a small molecule displaces them from the FK506-binding protein ligand-binding site. We demonstrate that CAPs are generally applicable to a range of short peptides, including a protease cleavage site, a dimerization-inducing heptapeptide, a nuclear localization signal peptide, and an opioid peptide, with a chemical dependence up to 156-fold. We show that the CAPs system can be utilized in cell cultures and multiple organs in living animals.
DOI: 10.1038/s41592-022-01697-8
Source: https://www.nature.com/articles/s41592-022-01697-8
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：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex
本期文章：《自然—方法学》：Online/在线发表
