Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How cells filter status updates

15.11.2017

Social media have become an indispensable part of our everyday life. We use them constantly to screen the latest news and share pre-selected information. The cells in our body do a similar thing. Information is pre-selected and transmitted to the immune system in order to fight against unwelcome invaders, such as viruses, bacteria, parasites or cancer. This pre-selection occurs by means of a highly complex molecular machine. Biochemists at Goethe University Frankfurt and the Max Planck Institute of Biophysics, in cooperation with researchers at Martin Luther University Halle-Wittenberg, have now unveiled the inner workings of this complex molecular machine.

Social media have become an indispensable part of our everyday life. We use them constantly to screen the latest news and share pre-selected information. The cells in our body do a similar thing. Information is pre-selected and transmitted to the immune system in order to fight against unwelcome invaders, such as viruses, bacteria, parasites or cancer.


Structure of the MHC-I peptide-loading complex in the membrane of the endoplasmic reticulum.

Image rights: Arne Möller (Max Planck Institute of Biophysics), Simon Trowitzsch and Robert Tampé (Goethe University Frankfurt)

This pre-selection occurs by means of a highly complex molecular machine. Biochemists at Goethe University Frankfurt and the Max Planck Institute of Biophysics, in cooperation with researchers at Martin Luther University Halle-Wittenberg, have now unveiled the inner workings of this complex molecular machine.

Status updates of each cell are transmitted from the cell’s interior to the immune system in the form of small protein fragments. These fragments are presented on the cell surface by specific proteins, known as MHC-I molecules.

Cancerous or infected cells can thus be quickly identified and eliminated. However, viruses and tumours can also trick the immune system and in so doing escape immune surveillance. In addition, ambiguous messages can lead to autoimmune diseases or chronic inflammation.

That is why it is particularly important to understand how this highly complex molecular machine in the cell’s interior selects the relevant protein fragments and coordinates the loading of MHC-I molecules. In the current issue of the renowned scientific journal NATURE, the researchers from Frankfurt and Halle provide first insights into the molecular architecture and inner workings of what is referred to as the MHC-I peptide-loading complex.

“We had to pull out all the stops to prepare this extremely fragile complex for structural analyses,” explains Dr. Simon Trowitzsch of the Institute of Biochemistry at Goethe University Frankfurt. “First of all, we expanded our biochemical toolbox and developed a viral molecular bait that allowed us to isolate the native MHC-I peptide-loading complex from the endoplasmic reticulum.”

“Thanks to groundbreaking advances in cryo-electron microscopy, which were recently awarded the Nobel Prize, we were able to look closely at the MHC-I peptide-loading complex - which is about a hundred thousand times smaller than a pinhead - and to determine its molecular structure,” reports Dr. Arne Möller from the Max Planck Institute of Biophysics.

The scientists can now deduce how the cell manages to generate information important for the immune system. Its structure shows how transport proteins in the membrane, folding enzymes and MHC-I molecules are working together precisely within a highly dynamic complex.

“Our research shows how the MHC-I peptide-loading complex filters out only those fragments of information which are actually needed by the immune system’s effector cells. These findings have solved a decades-old puzzle and allow us now to describe the antigen selection process with greater precision. This knowledge will help to further improve immunotherapies,” concludes Professor Robert Tampé from the Institute of Biochemistry.

Publication: Andreas Blees, Dovilė Janulienė, Tommy Hofmann, Nicole Koller, Carla Schmidt, Simon Trowitzsch, Arne Moeller & Robert Tampé: Structure of the human MHC-I peptide-loading complex, NATURE (Nov 6, 2017, First Release) doi:10.1038/nature24627

A picture can be downloaded from: www.uni-frankfurt.de/69093715

Caption: Structure of the MHC-I peptide-loading complex in the membrane of the endoplasmic reticulum.

Image rights: Arne Möller (Max Planck Institute of Biophysics), Simon Trowitzsch and Robert Tampé (Goethe University Frankfurt)

Further information: Professor Dr. Robert Tampé and Dr. Simon Trowitzsch, Institute of Biochemistry, Faculty of Biochemistry, Chemistry and Pharmacy, Riedberg Campus, Tel.: +49(0)69-798-29475, Tel.: +49(0)69-798-29273, tampe@em.uni-frankfurt.de, Trowitzsch@biochem.uni-frankfurt.de; Dr. Arne Möller, Max Planck Institute of Biophysics, Tel.: +49(0)69-6303-3057, arne.moeller@biophys.mpg.de.

Current news about science, teaching, and society in GOETHE-UNI online (www.aktuelles.uni-frankfurt.de)

Goethe University is a research-oriented university in the European financial centre Frankfurt The university was founded in 1914 through private funding, primarily from Jewish sponsors, and has since produced pioneering achievements in the areas of social sciences, sociology and economics, medicine, quantum physics, brain research, and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a "foundation university". Today, it is among the top ten in external funding and among the top three largest universities in Germany, with three clusters of excellence in medicine, life sciences and the humanities. Together with the Technical University of Darmstadt and the University of Mainz, it acts as a partner of the inter-state strategic Rhine-Main University Alliance. Internet: www.uni-frankfurt.de

Publisher: The President of Goethe University Editor: Dr. Anne Hardy, Referee for Science Communication, PR & Communication Department, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: (069) 798-13035, Fax: (069) 798-763 12531.

Tobias Lang | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-frankfurt.de

More articles from Life Sciences:

nachricht Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

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...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

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....

Im Focus: The “TRiC” to folding actin

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...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Staying in Shape

16.08.2018 | Life Sciences

Diving robots find Antarctic seas exhale surprising amounts of carbon dioxide in winter

16.08.2018 | Earth Sciences

Protein droplets keep neurons at the ready and immune system in balance

16.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>