Scientists at the Max Planck Institute (MPI) of Biochemistry recently succeeded in revealing the structure of the cellular protein degradation machinery (26S proteasome) by combining different methods of structural biology.
The "regulatory particle" (in blue) detects the proteins tagged with ubiquitin and prepares them for degradation. The "core particle" (in red) breaks the proteins down into their single components. Credit: Julio Ortiz / Copyright: MPI of Biochemistry
The results of collaboration with colleagues from the University of California, San Francisco and the Swiss Federal Institute of Technology Zurich (ETH Zürich) represent an important step forward in the investigation of the 26S proteasome. The findings have now been published in Proceedings of the National Academy of Sciences.
At any given point in time, cells may contain only the proteins that are needed at exactly this moment. Otherwise, undesirable reactions can occur which could cause cancer or other diseases. Furthermore, the proteins have to be folded correctly to fulfill their tasks. Misfolded proteins can clump into aggregates, and neurodegenerative diseases such as Alzheimer's or Parkinson's may be the consequence. In order to prevent this, several mechanisms in the body regulate the number of proteins in the cell and degrade proteins if necessary.
"Cellular waste disposal" – the 26S proteasome – plays an important role in protein degradation. First, misfolded and potentially dangerous proteins are tagged with molecules called ubiquitin. The 26S proteasome detects the tagged proteins and breaks them down into small fragments, which are then recycled. Scientists in the team of Wolfgang Baumeister, head of the research department "Molecular Structural Biology" at the MPI of Biochemistry, have now been able to reveal its structure.
Many puzzle pieces lead to one structure
"The structure of the 26S proteasome changes continuously," explained Friedrich Förster, head of the research group "Modeling of Protein Complexes" at the MPI of Biochemistry. "That is why until now it could not be explained by means of traditional approaches, such as only using X-ray crystallography. We had to combine different methods to be successful." Electron microscopy and mass spectrometry helped to reveal the general structure of the 26S proteasome. X-ray crystallography provided detailed insights into specific areas of the molecule. The researchers then used computer software to integrate the different data and generate an overall picture.
Based on these results, the researchers next want to find out how the different mechanisms of protein degradation work in detail. "We have already developed a hypothesis of how exactly the 26S proteasome detects tagged proteins and processes them," said Stefan Bohn, scientist at the MPI of Biochemistry. The complete elucidation of the 26S proteasome and its underlying mechanisms could also be of medical importance: "Cellular waste disposal" is a therapeutic target for cancer und neurodegenerative diseases.
Dr. Wolfgang Baumeister | EurekAlert!
Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
16.08.2018 | Life Sciences
16.08.2018 | Earth Sciences
16.08.2018 | Life Sciences