Nature Biotechnology
21, 936 - 940 (2003)
Published online: 13 July 2003; | doi:10.1038/nbt844
There is a Corrigenda (September 2003) associated with this Letters.
Targeting of proteins to membranes through hedgehog auto-processingSylvie Vincent1, Abraham Thomas2, Bradley Brasher2
& John D Benson31
GenPath Pharmaceuticals, 300 Technology Square, Cambridge, Massachusetts 02139, USA. 2
SelectX Pharmaceuticals, 44 Hartwell Avenue, Lexington, Massachusetts 02421, USA. 3
Novartis Institutes for Biomedical Research, 100 Technology Square, Cambridge, Massachusetts 02139, USA.
Correspondence should be addressed to John D Benson john.benson@pharma.novartis.comHedgehog proteins use an auto-processing strategy to generate cholesterol-conjugated peptide products that act as extracellular ligands in a number of developmental signaling pathways. We describe an approach that takes advantage of the hedgehog auto-processing reaction to carry out intracellular modification of heterologous proteins, resulting in their localization to cell membranes. Such processing occurs spontaneously, without accessory proteins or modification by other enzymes. Using the green fluorescent protein (GFP) and the product of the Hras as model proteins, we demonstrate the use of hedgehog auto-processing to process heterologous N-terminal domains and direct the resulting biologically active products to cell membranes. This system represents a tool for targeting functional peptides and proteins to cell membranes, and may also offer a means of directing peptides or other small molecules to components of cholesterol metabolism or regulation.
|
