Immune protein C4BP potentially suitable as transporter for drugs

Apr 26, 2013
Schematic of the "spider protein" C4BP. Credit: HZI / Schmelz

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 within the human body: more than sixty different proteins form one of the first countermeasures against invading pathogens. One of them is the C4b known as C4BP. It is involved in the immune defence against bacteria in the blood. How precisely such substance carries out its function or how it interacts with other molecules – this can only be predicted by scientists once they have identified the 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 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, at the Institute for 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.

Explore further: Bulletproof nuclei? Stem cells exhibit unusual absorption property

More information: Thomas Hofmeyer, Stefan Schmelz, Matteo T. Degiacomi, Matteo Dal Peraro, Matin Daneschdar, Andrea Scrima, Joop van den Heuvel, Dirk W. Heinz, Harald Kolmar, Arranged Sevenfold: Structural Insights into the C-Terminal Oligomerization Domain of Human C4b-Binding Protein, Journal of Molecular Biology, 2013, DOI: 10.106/j.jmb.2012.12.017

add to favorites email to friend print save as pdf

Related Stories

Why spiders don't drop off of their threads

Aug 17, 2011

It has five times the tensile strength of steel and is stronger then even the best currently available synthetic fibers: Spider thread. German scientists of the Technische Universitaet Muenchen and the Universitaet Bayreuth ...

Scientists watch proteins self-assemble

Jun 10, 2012

Enabling bioengineers to design new molecular machines for nanotechnology applications is one of the possible outcomes of a study by University of Montreal researchers that was published in Nature Structural an ...

Recommended for you

Researchers successfully clone adult human stem cells

Apr 18, 2014

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

Apr 18, 2014

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

User comments : 0

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Finnish inventor rethinks design of the axe

(Phys.org) —Finnish inventor Heikki Kärnä is the man behind the Vipukirves Leveraxe, which is a precision tool for splitting firewood. He designed the tool to make the job easier and more efficient, with ...

Making graphene in your kitchen

Graphene has been touted as a wonder material—the world's thinnest substance, but super-strong. Now scientists say it is so easy to make you could produce some in your kitchen.