Navigation Links
New look identifies crucial clumping of diabetes-causing proteins
Date:11/12/2013

MADISON People get type 2 diabetes. So do cats. But rats don't, and neither do dogs.

Subtle differences in the shape of proteins protect some and endanger others.

"All mammals make this same protein called amylin, and it only differs a little bit from species to species," says Martin Zanni, a University of WisconsinMadison chemistry professor. "The mammals that get type 2 diabetes, their amylin proteins aggregate in the pancreas into plaque that kills the cells around them. As a result, you can't make insulin."

Without insulin, hungry cells can't tap sugar in the bloodstream for energy, and high blood sugar levels cause type 2 diabetes and its complications stroke, nerve damage and kidney disease among them.

Animal species that don't get type 2 diabetes find a way to keep plaque from forming in their pancreas and disrupting insulin production. Describing how their amylin proteins differ may provide a target for new treatments for diabetes and other plaque-involved disease such as Alzheimer's and Parkinson's.

A study published today by Zanni and collaborators in the Proceedings of the National Academy of Sciences paints that target on small clumps of mis-folding proteins in the middle of the plaque formation process.

"For about 30 years, we thought this problem was solved, because a lot of experiments pointed to the middle part of amylin molecules as the cause," Zanni says.

Named for its amino acid structure, the FGAIL regions of amylin proteins were believed to lock together "like boards in a wood floor," Zanni says into rigid sheets. The sheets, called beta-sheets, break apart, forming the dangerous plaque.

But experiments published in 2007 showed that the FGAIL section of amylin is floppy and loose, like a loop of rope. "This result made no sense compared to the 30 years of prior studies," Zanni says. "Why should the small differences in the amylin protein of various mammals play such a deciding role if those differences are located in a flexible, floppy and forgiving region of the protein?"

Zanni and collaborators showed that the floppy FGAIL region can contribute to the formation of plaque, but first, the amylin proteins must clump together in an arrangement in which the FGAIL region is indeed a rigid beta-sheet.

"That 30-year-old hypothesis is partly correct: the FGAIL region does indeed form the beta-sheets, but only for a little while until those sheets are broken to make the flexible loop," Zanni says.

The intermediate clumping step is where animal species resistant to type 2 diabetes are making their move.

"Our results indicate that the proteins in rats, dogs and other animals do not stop the plaques themselves, but instead target this upstream step," Zanni says, "preventing the intermediate from forming and thereby the plaques as well."

Using a technique called two-dimensional infrared spectroscopy developed in Zanni's lab, the new study which included collaborators at the University of California, Irvine, University of Chicago, Argonne National Lab and State University of New York at Stony Brook provides the first picture containing specific details of what the intermediate clumps look like.

"Good drugs work by fitting into nooks and crannies," says Zanni, whose work is funded by the National Institutes of Health. "Thus, it is much easier to design a drug when the shape of the toxic protein is known, which is what our data is beginning to provide."


'/>"/>

Contact: Martin Zanni
zanni@chem.wisc.edu
608-262-4783
University of Wisconsin-Madison
Source:Eurekalert

Related biology news :

1. Plant DNA speaks English, identifies new species
2. 23andMe identifies 5 significant genetic associations for hypothyroidism
3. Collaborative research team identifies safe upper level for vitamin A consumption for puppies
4. UI professor identifies largest known crocodile
5. Research identifies specific bacteria linked to indoor water-damage and mold
6. Neiker-Tecnalia identifies antitumour proteins in the latex of the plant Euphorbia trigona
7. Study identifies pathway to enhance usefulness of EGFR inhibitors in lung cancer treatment
8. Study identifies how muscles are paralyzed during sleep
9. La Jolla institute identifies critical cell in fighting E. coli infection
10. BUSM study identifies receptors role in regulating obesity, type 2 diabetes
11. Research identifies mechanism responsible for eye movement disorder
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... 2017 KEY FINDINGS The global ... a CAGR of 25.76% during the forecast period of ... factor for the growth of the stem cell market. ... MARKET INSIGHTS The global stem cell market is ... geography. The stem cell market of the product is ...
(Date:3/30/2017)... YORK , March 30, 2017 Trends, ... type (physiological and behavioral), by technology (fingerprint, AFIS, iris ... voice recognition, and others), by end use industry (government ... and immigration, financial and banking, and others), and by ... Europe , Asia Pacific , ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Global ... to 2025" report to their offering. ... The Global Biometric Vehicle Access System Market ... the next decade to reach approximately $1,580 million by 2025. ... for all the given segments on global as well as regional ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... ... October 10, 2017 , ... San Diego-based team building and cooking events company, ... today. The bold new look is part of a transformation to increase awareness, ... significant growth period. , It will also expand its service offering from its signature ...
(Date:10/10/2017)... SANTA CRUZ, Calif. , Oct. 10, 2017 /PRNewswire/ ... SBIR grant from the NIH to develop RealSeq®-SC (Single ... preparation kit for profiling small RNAs (including microRNAs) from ... Cell Analysis Program highlights the need to accelerate development ... "New techniques for ...
(Date:10/9/2017)... (PRWEB) , ... October 09, 2017 , ... At its ... Dr. Christopher Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, has ... was a member of the winning team for the 2015 Breakthrough Prize in Fundamental ...
(Date:10/7/2017)...  The 2017 Nobel Prize in Chemistry recognizes ... Joachim Frank and Richard Henderson ... (cryo-EM) have helped to broaden the use ... The winners worked with systems manufactured by Thermo ... resolved, three-dimensional images of protein structures that lead ...
Breaking Biology Technology: