Recent advances in the optical control of protein function through genetic code expansion

Abstract

In nature, biological processes are regulated with precise spatial and temporal resolution at the molecular, cellular, and organismal levels. In order to perturb and manipulate these processes, optically controlled chemical tools have been developed and applied in living systems. The use of light as an external trigger provides spatial and temporal control with minimal adverse effects. Incorporation of light-responsive amino acids into proteins in cells and organisms with an expanded genetic code has enabled the precise activation/deactivation of numerous, diverse proteins, such as kinases, nucleases, proteases, and polymerases. Using unnatural amino acids to generate light-triggered proteins enables a rational engineering approach that is based on mechanistic and/or structural information. This review focuses on the most recent developments in the field, including technological advances and biological applications.

Probing the Subcellular Distribution of Phosphatidylinositol Reveals a Surprising Lack at the Plasma Membrane

“…However, none of the mutants we screened retained sufficient activity to yield DAG production upon recruitment, whilst also showing low basal activity before recruitment. We also attempted to incorporate caged lysine into the L. monocytogenes enzyme using unnatural amino acids (Courtney and Deiters, 2018), though were unable to obtain expression of the mutated enzyme.…”

Red-light-sensitive BODIPY photoprotecting groups for amines and their biological application in controlling heart rhythm

“…gene activation and silencing, 1 or protein interactions. 2 Because of many potential non-invasive applications with enhanced selectivity, light controlled activation of biologically active compounds, such as antibiotics, 3,4 anticancer agents, 5 neurotransmitters, 6 amino acids or proteins 7 and kinase inhibitors 8 is currently being explored. 9 Since their introduction by Engels and Schlaeger 10 for the protection of adenosine, PPGs have been extensively studied, and several key aspects have been determined as being crucial for their applicability in biological systems.…”

A High Avidity Biosensor Reveals PI(3,4)P2 is Predominantly a Class I PI3K Signaling Product

“…We found that expression of LepB led to substantial PI3P depletion from cells, and consequent swelling of the endosomal compartment that depends on this lipid for function (B.D.G and G.R.V.H., unpublished observations). Therefore, to induce acute LepB activity, we turned to an optogenetic approach that utilizes genetic code expansion to incorporate an unnatural, caged amino acid into the protein (Luo et al, 2014;Liu et al, 2017;Courtney and Deiters, 2018).…”