美国加州大学旧金山分校Tanja Kortemme课题组的一项最新研究，开发出模块化蛋白质感知-响应系统的计算设计策略。该研究于2019年11月22日发表于国际一流学术期刊《科学》。

研究人员报道了一种设计传感器-致动器蛋白的通用计算策略，其通过建立从头到异二聚体蛋白质与蛋白质界面的结合位点，并将配体传感通过拆分的报告分子偶联至模块驱动。

使用这种方法，研究人员设计了对法呢基焦磷酸（重要化合物生产中的代谢中间产物）有反应的蛋白质传感器。传感器在体外和细胞中均具有功能，工程结合位点的晶体结构与设计模型紧密匹配。这一计算设计策略为生物输出与新信号的连接开辟了广阔的渠道。

据悉，传感和响应信号是生命系统的基本能力，目前的研究尽管在新蛋白质结构的计算设计中取得了重大进展，但尚无用于工程化任意新蛋白质传感器的通用方法。

附：英文原文

Title: Computational design of a modular protein sense-response system

Author: Anum A. Glasgow, Yao-Ming Huang, Daniel J. Mandell, Michael Thompson, Ryan Ritterson, Amanda L. Loshbaugh, Jenna Pellegrino, Cody Krivacic, Roland A. Pache, Kyle A. Barlow, Noah Ollikainen, Deborah Jeon, Mark J. S. Kelly, James S. Fraser, Tanja Kortemme

Issue&Volume: 2019/11/22

Abstract: Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals.

DOI: 10.1126/science.aax8780

Source: https://science.sciencemag.org/content/366/6468/1024