Signaling in cells can occur through protein-protein interactions. Chen et al. describe the design of logic gates that can regulate protein association. The gates were built from small, designed proteins that all have a similar structure but where one module can be designed to interact specifically with another module. Using monomers and covalently connected monomers as inputs and encoding specificity through designed hydrogen-bond networks allowed the construction of two-input or three-input gates based on competitive binding. The modular control elements were used to regulate the association of elements of transcription machinery and split enzymes in vitro and in yeast cells.
Science, this issue p. 78
The design of modular protein logic for regulating protein function at the posttranscriptional level is a challenge for synthetic biology. Here, we describe the design of two-input AND, OR, NAND, NOR, XNOR, and NOT gates built from de novo–designed proteins. These gates regulate the association of arbitrary protein units ranging from split enzymes to transcriptional machinery in vitro, in yeast and in primary human T cells, where they control the expression of the TIM3 gene related to T cell exhaustion. Designed binding interaction cooperativity, confirmed by native mass spectrometry, makes the gates largely insensitive to stoichiometric imbalances in the inputs, and the modularity of the approach enables ready extension to three-input OR, AND, and disjunctive normal form gates. The modularity and cooperativity of the control elements, coupled with the ability to de novo design an essentially unlimited number of protein components, should enable the design of sophisticated posttranslational control logic over a wide range of biological functions.
- Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) – Science Magazine
- England coronavirus testing has not risen fast enough – science chief – The Guardian
- Coronavirus Tests Science’s Need for Speed Limits – The New York Times
- Trump Falsely Distorts New York Times COVID-19 Science Story – FactCheck.org
- This is the brightest supernova ever seen – Science Magazine
- Coronavirus Today: Science will save us – Los Angeles Times
- Italians stuck at home are measuring light pollution for ‘science on the balcony’ – TechCrunch
- ‘Oumuamua might be a shard of a broken planet – Science News
- College of Arts and Science converts thriving academic programs to departments – Vanderbilt University News