Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular Bodyguards for Immature Membrane Proteins

08.09.2015

During their formation within the cells, many proteins rely on the assistance of molecular protectors, so-called chaperones. They help the proteins to fold correctly and thus ensure the right final structure. The roles of chaperones in membrane protein folding have long remained unclear. Researchers at the Biozentrum, University of Basel, and at ETH Zurich have now shown how chaperones stabilize an immature bacterial membrane protein and guide it in the right folding direction, thus protecting it from misfolding. Their study was recently published in “Nature Structural & Molecular Biology”.

Cellular machines continuously produce long polypeptide chains, the proteins. In order to properly fulfill its cellular function, a protein must however first adopt its correct spatial structure. In each cell there are molecular helper proteins called chaperones. They take care of the immature proteins to help them in the folding process and thus preventing errors.


Chaperones (light blue) promote the insertion and folding of the bacterial membrane protein FhuA (yellow).

University of Basel, Biozentrum

The scientists led by Prof. Sebastian Hiller from the Biozentrum, University of Basel, and Prof. Daniel Müller from the Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich in Basel have discovered how two chaperones in the gut bacterium E. coli protect the membrane protein FhuA during transport and assist its insertion into the membrane.

Chaperones help insertion of membrane protein

... more about:
»Biozentrum »Bodyguards »ETH »bacteria »proteins »structure

Countless proteins, which transport nutrients and signaling molecules, are embedded in the outer membrane of bacteria. One of these membrane transporters is the protein FhuA. Via this protein, the bacteria take up vitally important iron but also antibiotics. But how does the very large, barrel-shaped FhuA protein reach the outer membrane intact? The scientists from the Biozentrum and the D-BSSE have investigated this process more deeply.

In order to reach its goal in the outer membrane, FhuA uses the help of several chaperones. Using structural analyses and single-molecule force spectroscopy, the researchers have now elucidated how these two chaperones stabilize the immature protein and prevent misfolding. “This process is extremely dynamic,” says Hiller.

“Under the protection of the chaperones, within a millisecond, FhuA constantly changes its structure. It thus explores energetically favorable conformations which enable the stepwise insertion and folding of individual protein segments into the membrane.” With the insertion of the final protein segment, FhuA acquires its mature and functional barrel structure. Left unprotected, FhuA would fold incorrectly and finally aggregate.

Protein chaos without chaperones

Chaperones are significantly involved in the formation of functional proteins. They play an important role in the correct folding of soluble proteins and furthermore are necessary for the insertion of membrane proteins into the bacterial outer membrane. Because several organelles in plant and animal cells are of bacterial origin, chaperones also protect their membrane proteins in a similar manner and assist during membrane insertion. The new findings are consequently of great relevance also for diseases caused by misfolded proteins such as Alzheimer's, Parkinson's or cystic fibrosis.

“It has been known for a long time that chaperones protect other proteins from misfolding and encourage them to fold correctly. Now, our work has succeeded in demonstrating – for the first time in biological membranes – how chaperones support the membrane proteins that are key to pharmaceutical research,” explains ETH Professor Daniel Müller. Until recently, these could almost only be investigated using artificial environments. However, this meant that there was barely any understanding of how proteins fold into a cell’s membrane.

“To give a loose analogy, until now it was like putting a cow on a sheet of ice in order to investigate its natural behaviour and then observing surprising reactions,” says Müller. “We now have a better understanding of how the cell incorporates its molecular machines into membranes so that they can perform their versatile duties.”

Original source

Johannes Thoma, Björn M Burmann, Sebastian Hiller & Daniel J Müller
Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins
Nature Structural & Molecular Biology (2015), doi: 10.1038/nsmb.3087

Further information

Prof. Sebastian Hiller, University of Basel, Biozentrum, tel. +41 61 267 20 82, email: sebastian.hiller@unibas.ch
Prof. Daniel J. Müller, ETH Zurich, Department of Biosystems Science and Engineering, tel. +41 61 387 33 07, email: daniel.mueller@bsse.ethz.ch

Katrin Bühler | Universität Basel
Further information:
http://www.unibas.ch

Further reports about: Biozentrum Bodyguards ETH bacteria proteins structure

More articles from Life Sciences:

nachricht Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel

nachricht Smelling the forest – not the trees
12.12.2018 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

New discoveries predict ability to forecast dementia from single molecule

12.12.2018 | Health and Medicine

CCNY-Yale researchers make shape shifting cell breakthrough

12.12.2018 | Physics and Astronomy

Pain: Perception and motor impulses arise in the brain independently of one another

12.12.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>