Of Science, Spectrometry, and Senseis

By Eric Sauter

A pair of new studies that goes a long way to explain the signaling mechanism of an essential plant hormone also highlights the role played by Graham West, a postdoctoral fellow in Professor Patrick Griffin’s Scripps Florida laboratory. The twin studies, published within a month of each other by the journals Science and Proceedings of the National Academy of Sciences, are the result of an international consortium of scientists in locations from Florida to Shanghai, with stops in Michigan, Illinois, and California along the way.

“Graham was basically responsible for doing the actual experimentation in our lab and interfacing with our multinational collaborators,” Griffin said. “Not only does the work show Graham’s productivity, it also demonstrates some of our technology is highly applicable and one of the best when applied to a variety of protein families.”

Both new studies focus on abscisic acid (ABA), an essential hormone and central regulator that protects plants from various environmental stresses by inhibiting their growth during periods of drought and salinity—problems that continue to plague food crops throughout the world. The studies (which actually began as a single paper but were split into two for issues of clarity), were spearheaded by Eric Xu of the Van Andel Institute in Michigan, who set out to solve the crystal structure of the molecular complex at the heart of the ABA signaling network.

While the Xu laboratory and their other global collaborators were handling the development of this crystal structure, they needed more—a better picture of the dynamics of these interactions—and for that they needed HDX, a technology that the Griffin lab has helped pioneer.

The technology, called hydrogen-deuterium (HDX) mass spectrometry, is used to measure the interaction of various molecules with specific receptors. HDX mass spectrometry is basically a mapping technique, which allows researchers to find the specific regions of the molecules that interact and to determine the structural changes that result from that interaction.

Because the ABA signaling structures can adopt a number of conformations, West said, the HDX technology provides unique insight into the dynamics of its mechanism, something crystallography can’t do.

“With these kinases there is one site that is indicative of activity—and with HDX we can zero in on the active site and show how these kinases lose or gain activity,” he said. “I think of the crystal structures as providing high-resolution snap shots and the HDX as the YouTube videos for the project.”

West, who is a member of the executive committee of the Scripps Florida Society of Research Fellows, came to Jupiter from Duke University in February 2010.

“I like the academic atmosphere at Scripps Florida,” he said, acknowledging the influence of both Griffin and Michael Chalmers, an associate scientific director in the Translational Research Institute whom West called his “sensei” in the laboratory.

Even in the context of the international attention that Scripps Florida attracts, the broad international scope of the recent collaboration was pretty amazing, West said.

“For being so global, it was a very open collaboration with rapid feedback, open sharing of data, and a lot of talking back and forth,” he said. “Of course, it was still a little more challenging than when your collaborators are just down the hall.”

The study, “Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases,” was published in the January 6, 2012 edition of Science (vol. 335 no. 6064). Its companion study, “Structural Basis for Basal Activity and Auto-Activation of ABA Signaling Snrk2 Kinases,” was published in the December 27, 2011 edition of PNAS (vol. 108 no. 52).

Send comments to: press@scripps.edu