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Hopkins scientists uncover 'tags' that force proteins to cell surface

rface, Shikano added randomly generated eight-building-block long tags onto one end of a particular protein. He then evaluated whether the protein ended up on the cell surface instead of remaining inside the cell. The researchers found three major classes of such tags, grouped according to similarities in their sequences of building blocks, and delved into the most potent of them.

By using a computer program developed by graduate student Brian Coblitz to probe proteins' sequences, the researchers discovered that, by fairly stringent criteria, roughly 4 percent of all human proteins contain SWTY or a very close relative. The eight-block-long tag itself is part of the so-called C-terminal end of these proteins, and its existence helps explain why some engineered proteins don't go where they're supposed to go, Li says.

"If you remove a small part of the very end of a protein, it seems unlikely to disrupt how the rest of the protein folds in a three-dimensional structure, but that's what most scientists think goes wrong if a protein doesn't go to the surface," says Li. "But now we know the problem might just be a faulty transportation signal."

Given that proteins can be thousands of building blocks long, the final eight building blocks may not seem to be very important. But Li chose this size to study in part because naturally occurring proteins were already known to use similar-size bits for recognition and signaling.

"The immune system uses ones that are seven to nine blocks long to identify viral proteins or other immune triggers," explains Li.

Also, the number of possible combinations of eight-block-long protein segments provides a "reasonable number" to sort through -- 25 billion or so -- given today's high throughput technologies. To make it even easier, Shikano developed a system that would separate the wheat from the chaff before the analysis began -- if the protein wasn't taken to the cell surface by the tag, the cell d
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Source:Johns Hopkins Medical Institutions


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