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29.01.2020 – 12:28

Technische Universität München

Guardian angel of the eye: Protective protein in the eye lens affects protein oxidation

TECHNICAL UNIVERSITY OF MUNICH

Corporate Communications Center

phone: +49 89 289 10510 - e-mail: presse@tum.de - web: www.tum.de

This text on the web: https://www.tum.de/nc/en/about-tum/news/press-releases/details/35874/

High resolution images: https://mediatum.ub.tum.de/1536982

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Guardian angel of the eye

Protective protein in the eye lens affects protein oxidation

The lens of the human eye comprises a highly concentrated protein solution, which lends the lens its great refractive power. Protective proteins prevent these proteins from clumping together throughout a lifetime. A team of scientists from the Technical University of Munich (TUM) has now uncovered the precise structure of the alpha-A-crystallin protein and, in the process, discovered an important additional function.

The refractive power of the human eye lens stems from a highly concentrated protein solution. These proteins are created during embryonic development and must then function for a whole life, as the lens has no machinery to synthesize or degrade proteins.

When lens proteins are damaged, the result is cataract - a clouding of the lens - or presbyopia. This is where protective proteins come in: They ensure that the proteins of the eye retain their form even under adverse environmental influences.

"The two protective proteins alpha-A and alpha-B-crystallin make up around 30 percent of the proteins in the human eye and are extremely important for the function of the lens," says Christoph Kaiser, first author of the publication in the journal Nature Structural and Molecular Biology.

Structure of a multifaceted protein

Attempts to determine the structure of alpha-A-crystallin were unsuccessful for over 40 years. The breakthrough came for a research team led by the TUM professors Sevil Weinkauf, professor of electron microscopy and Johannes Buchner, professor of biotechnology, by combining cryo-electron microscopy, mass spectrometry, NMR spectroscopy and molecular modeling.

"Alpha-A-crystallin is extremely multifaceted," says Sevil Weinkauf. "This makes it very difficult to determine its structure. It was only after developing a new strategy for data analysis that we were able to demonstrate that in solution it takes on different structures with 12, 16 or 20 subunits."

Protection against oxidation

The typical function of protective proteins is to help other proteins maintain their form when stressed, by high temperatures, for example. This is why they are also referred to as chaperones.

Alpha-A- and alpha-B-crystallin, too, have this function. In addition, human alpha-A-crystallin has two cysteine residues. The sulfur atoms in these residues can form disulfide bridges. In-depth biochemical studies have shown that this bridging has a significant impact on various properties of the protein molecule.

"A common theory is that the disulfide bridges result from damage to the protein, for example through oxygen," says Johannes Buchner. "Our results suggest that alpha-A-crystallin might play an active role in protecting other proteins from oxidation."

Motivation for further research

The research team's investigations demonstrate that oxidized alpha-A-crystallin can even transfer the existing disulfide bridge to other proteins. "This ability corresponds to that of a protein disulfide oxidase," says Christoph Kaiser. "Alpha-A-crystallin can thus influence the redox state of other lens proteins. This function also explains why roughly half of the alpha-A-crystallins in embryos already have such disulfide bridges."

"Around 35 percent of all cases of blindness can be attributed to cataracts, says Sevil Weinkauf. "The molecular understanding of the functions of eye lens proteins forms an essential basis for developing prevention and therapy strategies. The realization that alpha-A-crystallin also plays an important role in protecting against oxidation will now spawn further research."

Publication:

Christoph J. O. Kaiser, Carsten Peters, Philipp W. N. Schmid, Maria Stavropoulou, Juan Zou, Vinay Dahiya, Evgeny V. Mymrikov, Beate Rockel, Sam Asami, Martin Haslbeck, Juri Rappsilber, Bernd Reif, Martin Zacharias, Johannes Buchner & Sevil Weinkauf

The structure and oxidation of the eye lens chaperone alphaA-crystallin

Nature Structural & Molecular Biology vol. 26, 1141-1150 (2019) - DOI: 10.1038/s41594-019-0332-9

Link: https://www.nature.com/articles/s41594-019-0332-9

More information:

The research was funded by the German Research Foundation (SFB 1035 and Cluster of Excellence Center for Integrated Protein Science Munich) and the Wellcome Trust. Scientists from TU Munich, the Institute of Structural Biology at Helmholtz Zentrum München, the Institute for Biotechnology at the Technical University of Berlin and the Wellcome Center for Cell Biology at the University of Edinburgh (UK) participated in the research.

Related news:

https://www.tum.de/nc/en/about-tum/news/press-releases/details/31138/

https://www.tum.de/nc/en/about-tum/news/press-releases/details/32652/

https://www.tum.de/nc/en/about-tum/news/press-releases/details/32439/

High resolution Images:

https://mediatum.ub.tum.de/1536982

Contact:

Prof. Dr. Sevil Weinkauf

Professorship of Electron Microscopy

Technical University of Munich

Lichtenbergstr. 4, 85748 Garching, Germany

Tel.: +49 89 289 13517 - E-mail: sevil.weinkauf@ch.tum.de

Web: http://www.ch.tum.de/em

The Technical University of Munich (TUM) is one of Europe's leading research universities, with around 550 professors, 43,000 students, and 10,000 academic and non-academic staff. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with the TUM Asia campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006, 2012 and 2019 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. www.tum.de

More stories: Technische Universität München
More stories: Technische Universität München