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Those experiments hinted that one important steroid-related gene coded for a receptor protein called BRI1 that bound to the cell membrane. Their experiments indicated that another protein, a kinase called BIN2, appeared to act negatively in the steroid pathway to modify BES1 and BZR1 proteins, which targeted these proteins for turnover. In the presence of the steroids, BIN2 becomes inactivated by an unknown mechanism, thereby allowing BES1 and BZR1 to accumulate in the nucleus of the plant cell.

"Although we've known about BRI1 for almost eight years, we hadn't shown that it was actually a steroid receptor and not just part of a bigger complex," said Chory. To determine whether BRI1 was indeed the steroid receptor, co-author Hideharu Seto of RIKEN constructed synthetic versions of a functional steroid molecule that carried a telltale chemical tag. This synthetic steroid could also form a tight chemical bond with its natural target molecule when exposed to ultraviolet light. Experiments done in the Chory lab demonstrated that this synthetic steroid interacted directly with BRI1 and allowed her team to define a small region of BRI1 that is outside of the cell as the part of the molecule responsible for steroid binding. "These experiments enabled us to show definitively that BRI1 was actually binding to the steroid itself and wasn't just part of a bigger complex", said Chory.

Chory said that demonstrating that the steroid binds to BRI1 will open the way to new studies of the structural details of the interaction. "We will aim to obtain a three-dimensional structure of this receptor both with and without the steroid attached," she said. "And once we do that, we can begin to understand how this binding transmits signals inside the cell."

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
27-Jan-2005