Mechanism discovered for regulation of cell division

The study focused on three proteins that affect one of the central features of cell division, the mitotic spindle. One of the proteins, dynein, is a molecular motor that transports molecules during the development of the mitotic spindle and other structures in the cell. Two other proteins regulate dynein: dynactin, which is essential for linking dynein to other molecules; and NudE, whose depletion in experiments performed on mice produces a small brain and mental retardation.

“Protein molecules require a unique specific shape to recognize other proteins and do their biological function,” said Elisar Barbar, professor of biophysics at Oregon State and leader of the team that performed the research. “What is intriguing about the interplay of these three proteins is that the dynein segment that recognizes both dynactin and NudE does not have a specific shape. It belongs to a special class of proteins referred to as intrinsically disordered proteins. These proteins have multiple shapes and fluctuate quickly among them depending on alterations in environmental or cellular conditions.”

In work supported by the National Science Foundation and National Institutes of Health, the Barbar lab used a powerful tool ideally suited to reveal protein shapes, nuclear magnetic resonance spectroscopy, which can show multiple protein forms. The researchers used it to show that a segment of dynein changes shape depending on cellular conditions.

The shift in protein shapes has implications for the regulation of dynein and the formation of the mitotic spindle. The Barbar group found that the two dynein regulators bind to the same segment of dynein. However, dynactin binds to an additional disordered segment. By manipulating the length and chemical modification of this segment, one protein regulator can be selected over the other even when both are present in the same cellular compartment.

These results “offer a novel role for protein disorder in controlling cellular processes,” said Barbar.

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