Unravelling the mystery of misfolding prions

May 30, 2012 By Suzette Chan
Researchers used this specially designed "optical tweezers" apparatus to pull apart prion molecules with unprecedented precision.

(Phys.org) -- Researchers at the University of Alberta's physics department and the National Institute for Nanotechnology (NINT) are the first to map out the folding pathways of prions, malformed proteins that lead to diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (BSE, or "mad cow" disease) in cattle.

The team of researchers used specially designed optical tweezers to pull apart molecules of the protein PrP and map their motions with unprecedented precision.

"We are using tools from physics to help solve hard problems in biology," said Michael Woodside, a research officer at NINT who holds a cross-appointment as an assistant professor of physics at the U of A. "No one has ever directly mapped out the folding pathways that are available to the prion protein. By doing this, we get more detailed information about what are the likely states of the protein that should be targeted by therapeutics to prevent the disease."

Most strikingly, Woodside’s team found that the unfolded state of the prion may play a key role in the misfolding. "We don’t see evidence for the kind of partially folded, almost native intermediate states that have been postulated to lead to disease. Instead we find evidence for the importance of the unfolded state, which has been more neglected."

The optical tweezers used to pull on the protein molecules were developed by Woodside and his team to measure atomic-scale motions of the molecules in real time as they change structure. The apparatus is situated in the National Institute for Nanotechnology building on the UAlberta north campus.

Two physics students, three physics post-doctoral fellows and two NINT technicians, along with Woodside, worked on the experiment. The findings were recently published in Proceedings of the National Academy of Sciences. The lead authors were Hao Yu, a PhD candidate in physics, and Dr. Xia Liu, a post-doctoral fellow who is now a staff scientist at the Canadian Light Source.

Woodside is proud of his team, and he predicts the findings will lead to more investigations.

"This is the first study that has directly observed and characterized the formation of non-native (i.e., incorrect) structures in individual molecules that contain a single structural domain," he says. "Only a handful of studies have had sufficient spatial and temporal resolution to observe such effects, and they have not seen them."

Woodside adds, "There will be a lot to learn about what makes PrP special, with its unique and peculiar infectiousness, by comparing its folding to the folding of more ‘normal’ proteins when measured at the same level of precision."

Explore further: Bacterial protein called UmuD may prevent antibiotic resistance

add to favorites email to friend print save as pdf

Related Stories

New prion protein may offer insight into mad cow disease

Aug 16, 2007

Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. “Our team has defined a second prion protein called ‘Shadoo’, that exists in addition to the well-known ...

New prion protein may offer insight into mad cow disease

Aug 22, 2007

Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. Research led by Dr. David Westaway has led to the first discovery since 1985 of a new brain prion protein.

Is there more to prion protein than mad cow disease?

Sep 30, 2008

Prion protein, a form of protein that triggers BSE, is associated with other brain diseases in cattle, raising the possibility of a significant increase in the range of prion disease. Publishing their findings in the open ...

Scientists pioneer new method for watching proteins fold

Dec 22, 2011

(PhysOrg.com) -- A protein’s function depends on both the chains of molecules it is made of and the way those chains are folded. And while figuring out the former is relatively easy, the latter represents ...

Sequence and structure key to prion disease transmission

Jun 14, 2010

Prion diseases are lethal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE; commonly known as mad cow disease) in cows. A team of researchers, led ...

Mutant proteins result in infectious prion disease in mice

Dec 05, 2008

A worldwide group of scientists has created an infectious prion disease in a mouse model, in a step that may help unravel the mystery of this progressive disease that affects the nervous system in humans and animals. The ...

Recommended for you

SANS: a unique technique to look inside plants' leaves

Mar 26, 2015

Plants' leaves capture the sunlight and convert it into the energy used to produce nutrients for their activities. This process is accomplished thanks to the presence of the thylakoid membrane system. While ...

Silver shines as antibacterial for medical implants

Mar 24, 2015

There have been growing concerns in the global health care system about the eradication of pathogens in hospitals and other patient-care environments. Overuse of antibiotics and antimicrobial agents has contributed ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.