About a half-century ago, the electron microscope revealed the presence of tiny blob-like structures that form and move around inside cells, doing, well, nobody knows what.
The purpose of these ‘assemblages’ has eluded scientists to this day. Now, researchers from Georgetown University Medical Center in Washington D.C. and The Scripps Research Institute in La Jolla, Calif., are appealing to the wider scientific community from various disciplines to increase efforts to learn the function of the blobs, saying these mysterious structures could play an important role in cancer and other diseases. Their appeal is published in the journal Cell Biology.
The blob-like assemblages consist of changing cloud-like collections of proteins thought to be crucial to the life of a cell, said George Washington Medical Center in a statement.
“I want to know what these assemblages are doing in Ewing sarcoma, the disease I concentrate on—and I would think all other researchers who study human biology would want to know their functions in both health and disease,” says co-author Jeffrey Toretsky, M.D., a professor in the department of oncology and pediatrics at Georgetown Lombardi Comprehensive Cancer Center.
Toretsky joined with co-author Peter Wright, Ph.D., a professor of integrative structural and computational biology at The Scripps Research Institute, to put together an article containing everything that is known in biophysics and protein biochemistry about the mysterious blobs.
Diagram showing Assemblage formation. The protein molecules (yellow) aggregate to form assemblages and sequester strands of RNA (cyan). Image credit: Toretsky, J. & Wright, P., Journal of Cell Biology.
The authors write that these assemblages are usually made up of proteins that are “intrinsically disordered.” This means they do not assume a particular shape to fit neatly with other proteins a like lock and key. Oddly, the blobs seem to somehow locate each other and then form “gel-like assemblages” in a process called “phase separation” that can interact with other proteins, including RNA, the molecules that help regulate genes. Then, when the blobs finish doing whatever it is they do, the assemblages simply dissolve.
“It is only in the last five years that researchers have begun recognizing that proteins without fixed structures may have important transitional properties that change based upon their local abundance in cells,” said Toretsky, adding that if the assemblages play a role in disease states, they could be targeted with a small molecule.
“This review links together very basic biologic phenomena of protein interaction with the potential for new drug discovery,” says Toretsky. “It’s an exciting challenge.”
