In recent years, high-throughput discovery of macromolecular protein structures and complexes has played a major role in advancing a more systems-oriented view of protein interaction and signaling networks. The design of biological systems often employs structural information or structure-based protein design to successfully implement synthetic signaling circuits or for rewiring signaling flows. Here, we summarize the latest advances in using structural information for studying protein interaction and signaling networks, and in synthetic biology approaches. We then provide a perspective of how combining structural biology with engineered cell signaling modules--using additional information from quantitative biochemistry and proteomics, gene evolution, and mathematical modeling--can provide insight into signaling modules and the general design principles of cell signaling. Ultimately, this will improve our understanding of cell- and tissue-type-specific signal transduction. Integrating the quantitative effects of disease mutations into these systems may provide a basis for elucidating the molecular mechanisms of diseases.

The work was supported by the EU (PROSPECTS, grant agreement number 201648, and PRIMES, grant agreement number 278568)