Methods to identify modulators of tau protein structure
AssigneeRegents of the University of Minnesota
InventorsJonathan N. Sachs, Chih Hung Lo
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Abstract
The present disclosure provides methods for identifying compounds that cause structural changes in tau protein monomer and oligomer conformation. The methods include the use of cells that include tau proteins labeled with one or more chromophores, and exposing the cells to a test compound. The method further includes detecting a change in fluorescence resonance energy transfer (FRET) between the chromophores.
Claims20
A method for identifying a compound that alters fluorescence resonance energy transfer (FRET) of a protein comprising:
- providing a genetically engineered cell comprising two tau proteins,
- wherein a first tau protein comprises a first heterologous domain, wherein the first heterologous domain comprises a first probe,
- wherein a second tau protein comprises a second heterologous domain, wherein the second heterologous domain comprises a second probe;
- wherein the first and second tau proteins form an oligomer in the cell;
- contacting the cell with a test compound to form a mixture;
- and
- measuring fluorescence lifetime of the first probe, the second probe, or the combination thereof.
A method for identifying a compound that alters fluorescence resonance energy transfer (FRET) of a protein comprising:
- providing a genetically engineered cell comprising a tau protein,
- wherein the tau protein comprises two heterologous domains, wherein a first heterologous domain comprises a first probe, and wherein a second heterologous domain comprises a second probe, and
- wherein the tau protein forms an oligomer in the cell;
- contacting the cell with a test compound to form a mixture;
- and
- measuring fluorescence lifetime of the first probe, the second probe, or the combination thereof.
Dependencies are inferred from the claim text.