Membrane Protein Network Expands

A Canadian team of researchers reports the first comprehensive survey of interactions between membrane proteins and other proteins in yeast, including many that have never been identified before (Nature, DOI: 10.1038/nature11354). The interactions of membrane proteins have been consistently missed in previous surveys of protein-protein interactions. Because many membrane proteins are drug targets, the oversights represent a big knowledge gap.

The new study, led by Jack F. Greenblatt, Andrew Emili, and Shoshana J. Wodak of the University of Toronto and Elizabeth Conibear of the University of British Columbia, more than doubles the number of known interactions of yeast membrane proteins with other proteins.

A key obstacle to identifying interactions of membrane proteins has been getting the proteins out of the membranes, Greenblatt says. The process requires detergents that can solubilize the proteins without disrupting interactions.

“You can’t predict which detergent is going to be best for a given complex,” Greenblatt says. For the study, he and his coworkers purified each target membrane protein with each of three different detergent solutions. Using mass spectrometry, they then analyzed the purified membrane proteins and their interaction partners.

They identified 1,726 interactions, 1,110 of which had never been seen before, Greenblatt says. The other 616 interactions had previously been reported. They suspect that even more interactions remain to be found.

“Greenblatt and colleagues have plowed a rocky field for all of us who want to chart protein-protein interactions with membrane proteins,” says Steven P. Gygi, a professor of cell biology at Harvard Medical School. “They did nice work to define three detergent mixes that were used to vastly improve what we knew before about yeast membrane protein interactions.”