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Scripps research scientists solve structure of a critical innate immune system protein

Scientists at The Scripps Research Institute have solved the structure of a crucial human immune system molecule called TLR3, an acronym for Toll-like receptor three. In an upcoming issue of the journal Science, the protein is described as a large horseshoe-shaped coil composed of 23 leucine-rich repeats (LRRs).

The structure reveals details of TLR3 that have never been seen before, an essential step toward fully understanding the critical role this protein--and other TLRs--play in the human innate immune system to rapidly detect invading pathogens.

"We don't know functionally how TLR proteins work," says Professor Ian Wilson, D.Phil., who is a professor in the Department of Molecular Biology at The Scripps Research Institute and a member of the The Skaggs Institute for Chemical Biology. "but But the structure has given us great insights into experiments we can design to explore their function. In advance, we wouldn't have known where to look."

In addition to helping scientists better understand how TLRs work, the structure may also help scientists take steps toward improving human health, since TLRs are implicated in a number of diseases and, hence, constitute potential therapeutic targets.

Innate Immunity and Toll-Like Receptors

Humans, like all other organisms, are constantly challenged in a world filled with microbial pathogens. We are bathed in bacteria, confronted with fungi, pilloried with parasites, and invaded by viruses. And yet, most of the time, we survive.

We survive because we possess an ancient and crucial defense mechanism known as innate immune system, which is active in eukaryotic organisms as diverse as humans and fruit flies. Broadly speaking, the innate immune system works something like this. Certain cells have the ability to recognize foreign molecules such as components of membrane like LPS or other protein molecules unique to microorganisms . The presence of these pathogen-specific molecules act
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Source:Scripps Research Institute


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