Francis Crick Institute researchers have developed a way to
systematically relocate every protein in a cell to test whether
their location is critical for their function.
Dr Peter Thorpe of the Crick (currently based at Mill Hill)
said: "The locations of proteins within cells are assumed to be
critical for their function - but are they?
"We developed a technique that can test this by relocating every
protein within a living cell - much like rewiring an electric
circuit and and then testing whether it still works."
The scientists' method involves systematically fusing a target
protein with each of the other proteins expressed by a cell. The
resulting 'tug of war' can drag proteins to new locations within
the cell and forces interactions between proteins that may not
normally work together.
This allows researchers to then work out which of these forced
interactions and relocations affect how the cell behaves.
As proof of principle, Dr Thorpe and his colleague Guðjón
Ólafsson used this system in yeast to individually fuse all the
yeast proteins to a component of the kinetochore - the cellular
structure that pulls chromosomes apart as cells divide. This
allowed them to identify which proteins were important in
regulating the function of the kinetochore.
Dr Thorpe added: "This technology has the potential to relocate
every protein to compartments all over the cell, and so find out
how resilient the cell is to having the spatial arrangement of its
proteins shuffled."
The paper, Synthetic physical interactions map kinetochore regulators and
regions sensitive to constitutive Cdc14 localization, is
published in Proceedings of the National
Academy of Sciences.