Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein shaped like a spider

26.04.2013
Joint press release of the Helmholtz Centre for Infection Research and the Technische Universität Darmstadt
The immune protein C4BP is potentially suitable as a transporter for drugs.

The protein C4BP is similar to a spider in its spatial form with eight “arms”. The structure of the “spider body” has recently been described in detail by researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig and the Technische Universität Darmstadt. This leads the scientists to unconventional ideas – the protein is possibly suitable as a scaffold for the transport of active pharmaceutical substances, particularly biomolecules.
The researchers are publishing their results in the current edition of the international journal Journal of Molecular Biology.

The so-called complement system is a part of the innate immune defence within the human body: more than sixty different proteins form one of the first countermeasures against invading pathogens. One of them is the C4b binding protein known as C4BP. It is involved in the immune defence against bacteria in the blood. How precisely such protein substance carries out its function or how it interacts with other molecules – this can only be predicted by scientists once they have identified the spatial structure of the molecule. Structural biologists therefore examine the substance in its purest form with x-ray machines and are able to reconstruct the spatial design in a computer. Regarding the case of the recently-described C4BP, they found out that it has eight “arms” and thus resembles a spider to a certain degree. Seven of the “arms” are identical as “alpha chains”, while the eighth, a “beta chain” is different from the others. The spider body that holds these side chains together is called the oligomerisation domain. Its structure was of special interest to researchers, since it determines the spatial alignment of the “arms”.
The newly-described structure allows two possible variants. “However, there is one of these two possibilities that is more feasible because it is much more stable”, says Thomas Hofmeyer, PhD student at the Institute for Organic Chemistry and Biochemistry of TU Darmstadt and first author for the publication. And the C4BP is quite stable, as explained by the other first author Dr. Stefan Schmelz from the Department of Molecular Structural Biology of HZI: “Even boiling is not able to break down its form.” Usually, human proteins remain stable up to about 40°C. Higher temperatures are of course not found in the body, but the stability of C4BP has a completely different purpose: “As is the case with all components of the complement system, the C4b binding protein is present in blood plasma. The proteins are exposed to enormous shear forces in the blood stream”, explains Dr. Andrea Scrima, head of the junior research group “Structural Biology of Autophagy“ at HZI. Therefore, the protein needs a high stability in order to be able to withstand these forces.

The researchers now would like to make use of the spatial structure. Their discoveries have facilitated biochemical synthesis of the molecule. In the context of replication within a test tube, the researchers can undertake alterations in a targeted way: “Instead of the seven alpha chains, we could implement other biomolecules”, claims Prof. Harald Kolmar, director of the work group Applied Biochemistry at the Institute for Organic Chemistry and Biochemistry at the Technische Universität Darmstadt. “We can use the oligomerisation domain as a framework, in order to decorate it with drug molecules.” These could be vaccines, for example. Seven with one stroke, by means of the seven-fold binding capability. Bundled in this manner, more active ingredient could make its way to its target. The dosage could be reduced but the immune system would still be considerably stimulated. “It is thereby possible in the future that bottlenecks, limiting the supply of vaccine, could be avoided and side effects reduced”, says Kolmar.

Original publication:
Thomas Hofmeyer*, Stefan Schmelz*, Matteo T. Degiacomi, Matteo Dal Peraro, Matin Daneschdar, Andrea Scrima, Joop van den Heuvel, Dirk W. Heinz, Harald Kolmar, * contributed equally
Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein
Journal of Molecular Biology, 2013, DOI: 10.1016/j.jmb.2012.12.017

The Helmholtz Centre for Infection Research:
At the Helmholtz Centre for Infection Research (HZI) in Braunschweig, scientists are studying microbial virulence factors, host-pathogen interactions and immunity. The goal is to develop strategies for the diagnosis, prevention and therapy of human infectious diseases.

Schematic of the "spider protein" C4BP.
© HZI / Schmelz

http://www.helmholtz-hzi.de/en

The Technische Universität Darmstadt:
The Technische Universität (TU) Darmstadt is one of Germany’s leading technical universities. Its around 300 professors, 4,500 scientific and administrative employees and 25,000 students devote their talents and best efforts to the significant future research fields energy, mobility, communications and information technologies, housing and living.

http://www.tu-darmstadt.de

Dr. Jan Grabowski | Helmholtz-Zentrum
Further information:
http://dx.doi.org/10.1016/j.jmb.2012.12.017
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/protein_shaped_like_a_spider/

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Speed data for the brain’s navigation system

06.12.2016 | Health and Medicine

What happens in the cell nucleus after fertilization

06.12.2016 | Life Sciences

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>