Related Experiment Video
Updated: Jun 15, 2026
10:57
Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
Published on: February 16, 2015
Modularity of the Hrd1 ERAD complex underlies its diverse client range
Kazue Kanehara1, Wei Xie, Davis T W Ng
1Temasek Life Sciences Laboratory, National University of Singapore, Singapore.
The Journal of Cell Biology
|March 10, 2010
Summary
The Hrd1 complex manages endoplasmic reticulum-associated degradation (ERAD) pathways by recognizing misfolded proteins through specific signals. Its modular organization allows it to process diverse substrates, ensuring protein homeostasis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Protein Homeostasis
Background:
- Secretory protein folding is regulated by endoplasmic reticulum (ER) quality control.
- Misfolded proteins are targeted for degradation via ER-associated degradation (ERAD) pathways.
- E3 ubiquitin ligases are central to ERAD, orchestrating substrate recognition, ubiquitination, and translocation.
Purpose of the Study:
- To investigate the substrate specificity and modular organization of the Hrd1 complex in ERAD.
- To elucidate the roles of accessory factors in Hrd1-mediated protein degradation.
- To understand how the Hrd1 system recognizes diverse protein substrates.
Main Methods:
- Characterization of the Hrd1 complex and its associated factors (Usa1p, Der1p, Yos9p).
- Analysis of substrate recognition mechanisms, including glycan-dependent and independent signals.
- Investigation of the Hrd1 complex's role in degrading membrane and luminal proteins.
Main Results:
- The Hrd1 complex manages three distinct substrate classes.
- A core Hrd1 complex is essential for all classes, sufficient for some membrane proteins.
- Accessory factors Usa1p and Der1p enable processing of luminal substrates and glycan-independent signals.
- Yos9p extends substrate recognition to glycan-based degradation signals.
- The Hrd1 system indirectly recognizes misfolded proteins via embedded signals.
Conclusions:
- The Hrd1 complex exhibits a modular organization, allowing it to process topologically diverse substrates.
- Accessory factors confer substrate specificity, expanding the Hrd1 complex's degradation capabilities.
- The Hrd1 system's indirect recognition mechanism ensures efficient clearance of misfolded proteins.
Related Concept Videos
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:32Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...