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Split motifs

Only TRPC3 (WT) combined with PLC-1 generates a PH domain that binds lipids. SNYDER/MACMILLAN

Many more motifs may be lurking in proteins than previously expected. Randen Patterson (Pennsylvania State University, State College, PA), Damian van Rossum, Solomon Snyder (Johns Hopkins University, Baltimore, MD), and colleagues report that functional protein–lipid interaction motifs can be formed when partial motifs from two proteins unite.

The group's initial example of a split domain comes in the context of a Ca²⁺ entry system. In this system, neurotransmitters bind receptors that trigger production of inositol 1,4,5-trisphosphate (IP3), which in turn prompts release of intracellular Ca²⁺ stores and entry of extracellular Ca²⁺ through TRPC3 channels. Snyder and colleagues previously established that phospholipase C1 (PLC-1) was needed for this latter TRPC3 action, independent of PLC-1's enzymatic activity in generating IP3.

They now report that the binding of TRPC3 and PLC-1 to each other brings together two halves of a split PH domain, a motif associated with the binding of lipids and other proteins. Mutation of the partial PH domains changes the lipid-binding profile of the TRPC3–PLC-1 complex, and reduces the amount of TRPC3 at the plasma membrane 24 h after stimulation.

The phenomenon of split domains may be widespread. A modified search algorithm spotted not only the half-domains in TRPC3 and PLC-1 but also split domains in additional proteins. "It has opened up a whole new world," says Snyder. "It will amplify perhaps many-fold the number of protein recognition motifs." This profusion of motifs, he says, allows the cell to deliver on a promise: "Everything is hand delivered."

Reference:

van Rossum, D.B., et al. 2005. Nature. 434:99–104.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 265K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?