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Protein Networks02:26

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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
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Identification of Kinase-substrate Pairs Using High Throughput Screening
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An engineered protein-phosphorylation toggle network with implications for endogenous network discovery.

Deepak Mishra1,2,3, Tristan Bepler3,4,5, Brian Teague6

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

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|July 2, 2021
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Summary
This summary is machine-generated.

Researchers engineered a fast, synthetic bistable toggle switch in yeast using protein phosphorylation. This work also identified five new naturally occurring bistable biological networks, advancing synthetic biology and cellular engineering.

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Area of Science:

  • Synthetic biology
  • Molecular and cellular biology
  • Biochemistry

Background:

  • Fast, reversible reactions are key for engineering novel cellular behaviors.
  • Existing regulatory systems often rely on slower mechanisms.
  • Synthetic biological networks offer potential for rapid cellular control.

Purpose of the Study:

  • To engineer a synthetic bistable toggle switch in Saccharomyces cerevisiae using protein-protein phosphorylation.
  • To develop a computational framework for identifying endogenous bistable networks.
  • To experimentally validate newly discovered endogenous bistable networks.

Main Methods:

  • Construction of a synthetic toggle switch utilizing a cross-repression topology with 11 protein-protein phosphorylation elements.
  • Development of a computational framework to search endogenous protein pathways for bistable networks.
  • Experimental verification of identified endogenous networks for bistability.

Main Results:

  • Successfully created an ultrasensitive synthetic toggle switch in yeast that switches states within seconds and maintains long-term bistability.
  • Identified and experimentally verified five previously unreported endogenous biological networks exhibiting bistability.
  • Demonstrated the utility of the computational framework for discovering functional biological networks.

Conclusions:

  • Synthetic protein-protein networks can be rapidly engineered for sophisticated cellular regulation.
  • The developed computational framework aids in the discovery of endogenous networks with specific functions.
  • This research paves the way for designing fast sensing and processing systems in bioengineering.