Discovery of new protein could provide new understanding of male fertility

Bethesda, Md. Scientists have discovered a new enzyme involved in the degradation of proteins inside cells, a process that helps eliminate or recycle proteins that are no longer needed. The unexpected discovery, made by Marcus Groettrup, chair of the immunology department at the University of Constance, Konstanz, Germany, and colleagues, overthrows the idea that protein degradation is initiated by only one enzyme. Also, the new enzyme is very highly expressed in the testis, which could provide a new understanding of male fertility.

We essentially found that cleanup in the cell is not supervised by one but by two proteins, Groettrup says. It is important because everything we know about this cleanup process assumes that only one enzyme initiates it. The second protein we discovered may either share some functions with the first one or do totally different things.

The new study, to be published in the August 3 issue of the Journal of Biological Chemistry, was selected as a Paper of the Week by the journals editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Before being degraded, proteins are tagged with a small protein called ubiquitin. Three types of enzymes are involved in the tagging process. An enzyme called activating enzyme E1 first activates ubiquitin and binds to it. Then the ubiquitin is transferred to a second enzyme called ubiquitin-conjugating enzyme E2. And a third enzyme, called ubiquitin ligase E3 binds to both E2 and the protein to be degraded, so that E2 can transfer the ubiquitin to the protein. By binding to other ubiquitin-carrying E2 enzymes, E3 transfers many ubiquitins to the protein, signaling to the cell that the protein needs to be degraded.

Until now, only one type of E1 enzyme for ubiquitin has been known to exist in the human genome, while 34 E2 enzymes and 531 E3 enzymes have been discovered. Bec

Contact: Pat Pages
American Society for Biochemistry and Molecular Biology

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