Concepedia

Computational design of a modular protein sense-response system

Anum Glasgow, Yao-Ming Huang, Daniel J. Mandell, Michael C. Thompson, Ryan Ritterson, Amanda L. Loshbaugh, J. Pellegrino, Cody Krivacic, Roland A. Pache, Kyle A. Barlow,

Science · 2019 · 138 citations · 64 references

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TL;DR

Many signaling pathways rely on proteins that sense small molecules, yet designing protein‑based sense‑and‑respond systems remains difficult. They fused each monomer to a half of a split reporter, coupling ligand‑induced dimerization to reporter output. They designed heterodimer interface binding sites, demonstrating a general computational strategy that yields synthetic sensing systems with diverse outputs. Glasgow et al.

Abstract

Sense and respond Many signaling pathways start with cellular proteins sensing and responding to small molecules. Despite advances in protein design, creating a protein-based sense-and-respond system remains challenging. Glasgow et al. designed binding sites at the interface of protein heterodimers (see the Perspective by Chica). By fusing each monomer to one half of a split reporter, they linked ligand-driven dimerization to the reporter output. The computational design strategy provides a generalizable approach to create synthetic sensing systems with different outputs. Science , this issue p. 1024 ; see also p. 952