Mais design inteligente: como a célula 'identifica' e 'degrada' as proteínas defeituosas

terça-feira, janeiro 05, 2010

Researchers Identify Scaffold Regulating Protein Disposal

ScienceDaily (Jan. 5, 2010) — 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 Delbrück 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.

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 and functions and thus have quite different structures. For instance, there are water-soluble proteins inside the cell as well as water-insoluble proteins that are situated on or in the cell membrane.

Until now it remained unclear how the enzyme complex manages to recognize and mark such different types of proteins.
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Read more here/Leia mais aqui.

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Molecular Cell
Volume 36, Issue 5, 11 December 2009, Pages 782-793

Usa1 Functions as a Scaffold of the HRD-Ubiquitin Ligase

Sabine C. Horn1, Jennifer Hanna1, Christian Hirsch1, Corinna Volkwein1, Anja Schütz1, Udo Heinemann1, Thomas Sommer1, , and Ernst Jarosch1, ,

1 Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany


Received 4 February 2009; revised 10 July 2009; accepted 18 September 2009. Published: December 10, 2009. Available online 10 December 2009.
Summary

Protein quality control in the endoplasmic reticulum is of central importance for cellular homeostasis in eukaryotes. Crucial for this process is the HRD-ubiquitin ligase (HMG-CoA reductase degradation), which singles out terminally misfolded proteins and routes them for degradation to cytoplasmic 26S-proteasomes. Certain functions of this enzyme complex are allocated to defined subunits. However, it remains unclear how these components act in a concerted manner. Here, we show that Usa1 functions as a major scaffold protein of the HRD-ligase. For the turnover of soluble substrates, Der1 binding to the C terminus of Usa1 is required. The N terminus of Usa1 associates with Hrd1 and thus bridges Der1 to Hrd1. Strikingly, the Usa1 N terminus also induces oligomerization of the HRD complex, which is an exclusive prerequisite for the degradation of membrane proteins. Our data demonstrate that scaffold proteins are required to adapt ubiquitin ligase activities toward different classes of substrates.

Author Keywords: Proteins

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NOTA CAUSTICANTE DESTE BLOGGER:

Ao considerar o fato, Fato, FATO da evolução, tenha sempre em mente que Darwin nem sequer sabia direito o que era uma 'simples' célula...

Fui, nem sei por que, cada vez mais convencido do design inteligente!!!