How does a cell manage to identify and degrade the diverse types of defective proteins and thus protect the body against serious diseases? The researchers Sabine C. Horn, Professor Thomas Sommer, Professor Udo Heinemann and Dr. Ernst Jarosch of the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now found a crucial piece in this puzzle. In an enzyme complex that plays a critical role in the quality control of proteins, they discovered a scaffold regulating the identification and disposal of various defectively produced proteins. (Molecular Cell, doi: 10.1016/j.molcel200910.015)*.
Proteins are the building materials and the machinery of life. They are found by the thousands in a cell and carry out vital tasks in the organism.
The production site of many of the proteins is located in a cell organelle called the endoplasmic reticulum (ER). Here the proteins are produced, folded and routed to their destination.
However, during protein production errors can occur: during the process proteins can be folded in the wrong way. Older proteins may also accumulate defects due to environmental stress.
They can lose their original structure and thus fail to carry out their function and may possibly even cause damage. Diseases can develop such as Alzheimer's, Parkinson's or cystic fibrosis. Defective proteins must therefore be detected in the cell and disposed of.
Protein quality control: rejects receive a molecular tag
Proteins run through a quality control process in the cell. For the identification of defective proteins, an enzyme complex the HRD-ubiquitin ligase plays a key role.
It functions like a kind of tagging machine: If it recognizes the protein as defective, it tags it with a molecule, the protein ubiquitin, thus marking it for disposal.
Great demands are placed on the HRD-ubiquitin ligase, because proteins adapt to their cellular locations an
|Contact: Barbara Bachtler|
Helmholtz Association of German Research Centres