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Biological Chemistry

Technique Adds Proteins To Membranes At Specific Sites And Times

Biomodification: Lipid, linker, and photocaging give researchers exquisite control over accessorizing cell membranes and vesicles

by Stu Borman
April 16, 2015 | APPEARED IN VOLUME 93, ISSUE 16

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Credit: J. Am. Chem. Soc.
A SNAP-tag (green Pac-Man symbol) carrying a protein of interest (not shown) reacts with and displaces benzylguanine (left) on derivatized lipids (orange) added to a phospholipid membrane (blue).
09316-notw6-SNAP-690.jpg
Credit: J. Am. Chem. Soc.
A SNAP-tag (green Pac-Man symbol) carrying a protein of interest (not shown) reacts with and displaces benzylguanine (left) on derivatized lipids (orange) added to a phospholipid membrane (blue).

Researchers have developed the first technique that covalently attaches proteins at specific locations and times on phospholipid membranes or synthetic vesicles.

Cellular processes such as signaling, metabolism, and division require control over where and when proteins attach to membranes. The ability to design protein-coupled membranes or cells in a space- and time-controlled manner could aid research on such processes and lead to artificial cells with novel functions.

It has been possible to link proteins covalently to membranes with either spatial or temporal control in the past, but Neal K. Devaraj and coworkers at the University of California, San Diego, have now made it possible to do both simultaneously (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b00040).

The researchers “photocage” benzylguanine-modified lipids—by attaching a chemical group that prevents benzylguanine from reacting—and embed the lipids in a synthetic membrane or vesicle or a membrane on live cells. Shining a micrometer-sized beam of ultraviolet light onto the membrane at specific times and locations removes the photocage, permitting benzylguanine to react with protein-conjugated linking agents called SNAP-tags. The reaction connects the proteins to the membrane surface via the SNAP-tag linkers at selected times and with micrometer spatial resolution.

The technology is not currently ideal for labeling membranes inside live cells, such as those on cell organelles, because the modified lipids don’t permeate cells well.

“This work nicely demonstrates that the lipid-anchor strategy and its photocaged version can be used to direct proteins” to specific parts of membranes at specific times, says Shinya Tsukiji of Nagaoka University of Technology, in Japan, whose group develops synthetic tools to study and control cell functions. “Such an ability will become a valuable new tool for various applications—in particular, creating artificial cells whose structures and functions can be spatiotemporally regulated.”

Devaraj notes that the system “could be used for the study and reconstitution of enzymatic pathways, membrane curvature, cell division, and numerous other membrane-protein-dependent processes. The technique is not currently being commercialized and is freely available.”

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