普里昂

madtoyUID: 114985

普里昂   
整理日期：2002-6-14  文章分类目：EAG3200206142000
整理人：dsny   来源：寄托天下SUB主题乐园

　

介绍一下：
A new snapshot of the healthy human prion protein shows that it likes to pair up with a pal. The fact that the protein prefers to couple up may help to explain how abnormal prions cause degenerative brain conditions such as variant Creutzfeldt-Jacob disease (vCJD), the human form of bovine spongiform encephalopathy.

Previous images had cast the human prion as more of a singleton1. This provided few clues to how infectious prions might twist healthy ones out of shape and encourage them to clump - the preferred explanation for how transmissible spongiform encephalopathies such as vCJD arise.

Individual prions couple up by wrapping an armlike structure around each other, Vivien Yee of the Cleveland Clinic Foundation in Cleveland, Ohio and her colleagues have found2. This process, called three-dimensional domain swapping, "might be causing prions to form aggregates," says Yee.

A mutated prion could cause many individual proteins to link into chains, like a group of people joining hands, explains Yee. Other disease-causing, prion-like proteins occur in pairs known as dimers. Researchers had reasoned that as these couples go in for three-dimensional domain swapping, prions might be tricked into forming aggregates too3,4.

Yee's team deduced the structure of prion protein using X-ray crystallography, which requires a crystal made from a solution of the protein. Yee suspects that previous attempts to make crystals failed because human prions occur singly in solution. Her team were lucky enough to find a rare prion dimer in solution, and grew their crystal from that.

If the dimer structure turns out to be correct it would be "amazing," says Bruno Oesch, co-founder of Prionics AG, makers of diagnostic kits for prion diseases. "We hypothesized that natural [human prion] might be a dimer but there wasn't any proof," he says.

The parts of the protein involved in three-dimensional domain swapping could be potential targets for drugs to treat prion disease. "Fitting a small molecule in there that disrupts this interaction might be a significant advance in terms of therapy," says Oesch.