New findings on protein misfolding

September 18, 2012

Misfolded proteins can cause various neurodegenerative diseases such as spinocerebellar ataxias (SCAs) or Huntington's disease, which are characterized by a progressive loss of neurons in the brain. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, together with their colleagues of the Université Paris Diderot, Paris, France, have now identified 21 proteins that specifically bind to a protein called ataxin-1. Twelve of these proteins enhance the misfolding of ataxin-1 and thus promote the formation of harmful protein aggregate structures, whereas nine of them prevent the misfolding.

Proteins only function properly when the chains of , from which they are built, fold correctly. Misfolded proteins can be toxic for the cells and assemble into insoluble aggregates together with other proteins. Ataxin-1, the protein that the researchers have now investigated, is very prone to misfolding due to inherited that cause . The reason for this is that the amino acid glutamine is repeated in the of ataxin-1 very often - the more glutamine, the more toxic the protein. Approximately 40 repeats of glutamine are considered to be toxic for the cells.

Now, Dr. Spyros Petrakis, Dr. Miguel Andrade, Professor Erich Wanker and colleagues have identified 21 proteins that mainly interact with ataxin-1 and influence its folding or misfolding. Twelve of these proteins enhance the toxicity of ataxin-1 for the , whereas nine of the identified proteins reduce its toxicity.

Furthermore, the researchers detected a common feature in the structure of those proteins that enhances toxicity and aggregation. It is a special structure scientists call "coiled-coil-domain" because it resembles a double twisted spiral or helix. Apparently this structure promotes aggregation, because proteins that interact with ataxin-1 and have this domain enhance the toxic effect of mutated ataxin-1. As the researchers said, this structure could be a potential target for therapy: "A careful analysis of the molecular details could help to discover drugs that suppress toxic processes."

Explore further: Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too

More information: Identification of Human Proteins That Modify Misfolding and Proteotoxicity of Pathogenic Ataxin-1, PLoS Genetics, doi: 10.1371/journal.pgen.1002897

Related Stories

Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too

June 21, 2011
A team of scientists, led by researchers at the University of California, San Diego School of Medicine, have uncovered a novel mechanism regulating gene expression and transcription linked to Spinocerebellar ataxia 7, an ...

Scientists develop algorithm to understand certain human diseases

June 16, 2011
(Medical Xpress) -- Patricia Clark, the Rev. John Cardinal O’Hara, C.S.C. Associate Professor of Chemistry and Biochemistry at the University of Notre Dame, and Bonnie Berger, professor of applied mathematics at the ...

A natural dye obtained from lichens may combat Alzheimer's disease

December 2, 2011
A red dye derived from lichens that has been used for centuries to color fabrics and food appears to reduce the abundance of small toxic protein aggregates in Alzheimer's disease. The dye, a compound called orcein, and a ...

Recommended for you

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

Scientists identify key regulator of male fertility

September 19, 2017
When it comes to male reproductive fertility, timing is everything. Now scientists are finding new details on how disruption of this timing may contribute to male infertility or congenital illness.

New assay leads to step toward gene therapy for deaf patients

September 18, 2017
Scientists at Oregon State University have taken an important step toward gene therapy for deaf patients by developing a way to better study a large protein essential for hearing and finding a truncated version of it.

Genomic recycling: Ancestral genes take on new roles

September 18, 2017
One often hears about the multitude of genes we have in common with chimps, birds or other living creatures, but such comparisons are sometimes misleading. The shared percentage usually refers only to genes that encode instructions ...

0 comments

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.