Navigation Links
Research offers new way to target shape-shifting proteins
Date:8/28/2011

A molecule which can stop the formation of long protein strands, known as amyloid fibrils, that cause joint pain in kidney dialysis patients has been identified by researchers at the University of Leeds.

The discovery could lead to new methods to identify drugs to prevent, treat or halt the progression of other conditions in which amyloid fibrils play a part, including Alzheimer's, Parkinson's and Type II diabetes.

The research, funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust, is published today (August 28) in Nature Chemical Biology.

The team from Leeds' Astbury Centre for Structural Molecular Biology and Faculty of Biological Sciences found that an antibiotic known as Rifamycin SV was able to prevent the protein β2microglobulin (β2m) from forming into fibrils. β2m is known to accumulate in renal dialysis patients and forms fibrils within the joints, causing extreme pain and arthritis.

By using a specialised analytical technique called ion mobility spectrometry-mass spectrometry (IMS-MS), the researchers were able to see at what stage of the process Rifamycin SV prevented amyloid fibril formation. They believe the technique could enable potential drugs to be identified for the many other proteins which form amyloid fibrils, linked to a wide range of human disorders.

"Traditional drug design for diseases like Alzheimer's is incredibly difficult because the proteins you're trying to target are changing shape and structure all the time," explains University of Leeds Professor of Structural Molecular Biology, Sheena Radford. "It's like trying to consistently pick out one bead of a particular shape from box of potentially millions of similar beads. This new technique allows us to see the shape of the protein as it changes, so we can more easily identify exactly which part we need to target."

In their normal, folded state, proteins are unable to link together to form long fibrillar assemblies, but if they unfold, they expose areas where they can bind to each other. Initially they form small groups of two, three or four proteins, and then these link into long strands, which twist together to form fibrils.

Most analytical techniques can only show the mass of the protein or its make-up in terms of amino acids, neither of which changes as the protein unfolds. Others are unable to look at individual molecules within complex mixtures. However, IMS-MS can measure the mass and shape of a protein, allowing researchers to watch the unfolding process and the aggregation into small groups and then assembly into the fibril and to find which of these species is able to bind a ligand and stop the assembly process.

In the research published today, researchers found that Rifamycin SV stopped the formation of protein fibrils by binding to an unfolded protein molecule with a particular shape, enabling for the first time, an unfolded protein of a particular shape to be identified as a target for the design of new inhibitors of fibril assembly.

"We're fortunate to be one of the few universities in the UK able to use IMS-MS to study amyloid fibril formation," says Professor of Biomolecular Mass Spectrometry, Alison Ashcroft, who specialises in this type of analysis. "Although fibrils take years to develop in the body, we are able to 'grow' them in hours in the lab. By using IMS-MS to help us map exactly how they are formed, we can better understand the mechanism by which it happens and we hope find ways to stop it."


'/>"/>

Contact: Abigail Chard
abigail@campuspr.co.uk
44-079-604-48532
University of Leeds
Source:Eurekalert

Related biology news :

1. Wistar Institute researcher receives New Innovator award from NIH
2. NC State researchers get to root of parasite genome
3. White Mountain Research Station to host climate change conference
4. Stevens awarded $1M for advanced biofuels research
5. Researchers find animal with ability to survive climate change
6. Researchers find an essential gene for forming ears of corn
7. Researchers note differences between people and animals on calorie restriction
8. Researcher working on destruction of chemical weapons
9. Researchers study acoustic communication in deep-sea fish
10. Researchers discover that growing up too fast may mean dying young in honey bees
11. The Rett Syndrome Research Trust launches operations
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/20/2017)... Delta (NYSE: DAL ) customers now can use fingerprints instead ... National Airport (DCA). ... Delta launches biometrics to board aircraft at Reagan Washington National Airport ... Delta,s biometric boarding pass experience that launched in ... the boarding process to allow eligible Delta SkyMiles Members who are enrolled ...
(Date:5/23/2017)... , May 23, 2017  Hunova, the first robotic gym for the ... been officially launched in Genoa, Italy . The first ... and the USA . The technology was developed ... market by the IIT spin-off Movendo Technology thanks to a 10 million ... News Release, please click: ...
(Date:4/24/2017)... Janice Kephart , former 9/11 ... Partners, LLP (IdSP) , today issues the following ... March 6, 2017 Executive Order: Protecting the ... be instilled with greater confidence, enabling the reactivation ... applications are suspended by until at least July ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... , ... October 10, 2017 , ... Dr. Bob Harman, ... his local San Diego Rotary Club. The event entitled “Stem Cells ... and had 300+ attendees. Dr. Harman, DVM, MPVM was joined by two human ...
(Date:10/10/2017)... ... 10, 2017 , ... The Pittcon Program Committee is pleased ... scientists who have made outstanding contributions to analytical chemistry and applied spectroscopy. Each ... leading conference and exposition for laboratory science, which will be held February 26-March ...
(Date:10/9/2017)... ... October 09, 2017 , ... The Giving Tree Wellness ... targeting the needs of consumers who are incorporating medical marijuana into their wellness ... Arizona. , As operators of two successful Valley dispensaries, The Giving Tree’s two ...
(Date:10/7/2017)... 6, 2017  The 2017 Nobel Prize in ... Jacques Dubochet, Joachim Frank and ... cryo-electron microscopy (cryo-EM) have helped to broaden ... biology community. The winners worked with systems manufactured ... produce highly resolved, three-dimensional images of protein structures ...
Breaking Biology Technology: