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:11/24/2016)... -- Cercacor today introduced Ember TM Sport Premium ... measure hemoglobin, Oxygen Content, Oxygen Saturation, Perfusion Index, ... approximately 30 seconds. Smaller than a smartphone, using only ... key data about their bodies to help monitor these ... Hemoglobin carries oxygen to muscles. When hemoglobin and ...
(Date:11/22/2016)... 22, 2016   MedNet Solutions , an innovative ... of clinical research, is pleased to announce that the ... and Life Sciences Awards as "Most Outstanding in ... unprecedented year of recognition and growth for MedNet, which ... years. iMedNet ™ , MedNet,s ...
(Date:11/19/2016)... Nov. 18, 2016 Securus Technologies, a leading ... public safety, investigation, corrections and monitoring, announced today that ... ICSolutions, to have an independent technology judge determine who ... modern high tech/sophisticated telephone calling platform, and the best ... they do most of what we do – which ...
Breaking Biology News(10 mins):
(Date:11/30/2016)... ... November 30, 2016 , ... Energetiq ... applications, introduces the 5th generation, ultra-bright, Laser-Driven Light Source, the EQ-77, at the ... (LDLS™) technology, the EQ-77 offers higher radiance and irradiance from a truly broadband ...
(Date:11/30/2016)... Carolina (PRWEB) , ... November 30, 2016 , ... On ... names and symbols for four elements: nihonium (Nh), moscovium (Mc), tennessine (Ts), and ... period of public review, the names earlier proposed by the discoverers have been approved ...
(Date:11/30/2016)... Toronto, ON (PRWEB) , ... November 30, 2016 ... ... focused on discovery and development of precision treatments for neurodegenerative diseases, today announced ... disease (AD) (announced on November 3, 2016) blocked propagation of toxic, prion-like forms ...
(Date:11/30/2016)... -- Teil einer Investition von 5 Millionen ... ... Aptuit LLC hat heute bekannt gegeben, ... neuartige Substanzen haben die Prüfsammlung auf über 400.000 erhöht. ... Entdeckungsfähigkeiten des Unternehmens zu erweitern. Die Ausweitung, die durch ...
Breaking Biology Technology: