How Some Enzymes Involved in the Handling of Defective Proteins
The 2004 Nobel Prize in Chemistry went to scientists who found the protective program of ubiquitin-mediated protein degradation.
Now a group of scientists found some enzymes that got involved in the degradation of defective proteins for the first time.
It is well known that many cells are produced in cell organelle, the endoplasmic reticulum (ER). In the ER, there is a special process for protein degradation—ER-associated degradation (ERAD). The process is quite common. This system contains a number of enzymes that cooperate to ensure that a defective protein is marked with molecule ubiquitin. This process is ubiquitylation. A chain of four to six molecules serves as degradation signal. A protein tagged with such a molecular chain is transported to the proteasome, the protein-cleaving machinery of the cell, where it is separated into its components.
To facilitate the attachment of a ubiquitin chain to a defective protein, several enzymes are needed. Some of these enzymes are anchored in the membrane of the ER, others such as Ubc7 swim freely inside the cell. A factor called CUE1 is responsible for recruiting Ubc7 and escorting it to the enzymes at the membrane. To achieve this, it has a domain which binds specifically to Ubc7. Another domain of the factor is the so-called CUE domain. The researchers studied its function in yeast cells.
The CUE domain is a ubiquitin-binding domain (UBD). UBDs bind to specific ubiquitin patterns. The CUE domain of the factor Cue1 binds to ubiquitin chains that are linked together via a specific building block of the individual ubiquitin molecules. These chains subsequently serve as a degradation signal for proteins.
In addition, the researchers found that the CUE domain has a direct impact on the length of the ubiquitin chains: If the CUE domain was lacking or limited in its function due to a mutation, the ubiquitin chains developed more slowly and were shorter in length. Apparently, the CUE domain stabilizes the ubiquitin chains, allowing additional ubiquitin molecules to be attached more easily.
In yeast cells, the researchers found that the CUE domain of Cue1 in this way actually affects how effectively the ERAD system can degrade proteins, thus it is speculated that CUE domain might be used specifically for the disposal of proteins which are bound to the ER membrane.
The result showed that a ubiquitin-binding domain can also regulate the formation of ubiquitin chains.
Article Link: How Some Enzymes Involved in the Handling of Defective Proteins
