Protein shaped like a spider

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

2013-04-26

(Press-News.org) This press release is available in German.

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.

INFORMATION:

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. 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

ELSE PRESS RELEASES FROM THIS DATE:

New excavations indicate use of fertilizers 5,000 years ago

2013-04-26

Researchers from the University of Gothenburg, Sweden, have spent many years studying the remains of a Stone Age community in Karleby outside the town of Falköping, Sweden. The researchers have for example tried to identify parts of the inhabitants' diet. Right now they are looking for evidence that fertilisers were used already during the Scandinavian Stone Age, and the results of their first analyses may be exactly what they are looking for. Using remains of grains and other plants and some highly advanced analysis techniques, the two researchers and archaeologists ...

Computer scientists suggest new spin on origins of evolvability

2013-04-26

Scientists have long observed that species seem to have become increasingly capable of evolving in response to changes in the environment. But computer science researchers now say that the popular explanation of competition to survive in nature may not actually be necessary for evolvability to increase. In a paper published this week in PLOS ONE, the researchers report that evolvability can increase over generations regardless of whether species are competing for food, habitat or other factors. Using a simulated model they designed to mimic how organisms evolve, the ...

Sea surface temperatures reach highest level in 150 years

2013-04-26

Sea surface temperatures in the Northeast Shelf Large Marine Ecosystem during 2012 were the highest recorded in 150 years, according to the latest Ecosystem Advisory issued by NOAA's Northeast Fisheries Science Center (NEFSC). These high sea surface temperatures (SSTs) are the latest in a trend of above average temperature seen during the spring and summer seasons, and part of a pattern of elevated temperatures occurring in the Northwest Atlantic, but not seen elsewhere in the ocean basin over the past century. The advisory reports on conditions in the second half of ...

Federally funded research & development centers employed more than 3,000 postdoctoral researchers

2013-04-26

According to a recent report released by the National Science Foundation, 22 of the nation's 39 federally funded research and development centers (FFRDCs) employed 3,011 postdocs in 2010, the year the latest data are available. Three out of every four postdocs employed in the FFRDCs in 2010 were men. Foreign nationals on temporary visas made up 60 percent of all postdocs employed in FFRDCs. Men constituted a higher percentage of foreign nationals than of U.S. citizens and permanent residents--78 percent versus 72 percent. Among U.S. citizens and permanent residents, ...

National survey highlights perceived importance of dietary protein to prevent weight gain

2013-04-26

AUDIO: Atkins Diet, Zone Diet, South Beach Diet, etc. Chances are you have known someone who has tried a high protein diet. Noel Aldrich, Ph.D., University of Minnesota, discusses a new... Click here for more information. Philadelphia, PA, April 26, 2013 – Atkins Diet, Zone Diet, South Beach Diet, etc., etc., etc. Chances are you have known someone who has tried a high protein diet. In fact, according to the International Food Information Council Foundation, 50% of consumers ...

Battery of tests on cancer cells shows them as 'squishy,' yet tactically strong

2013-04-26

TEMPE, Ariz. – A team of student researchers and their professors from 20 laboratories around the country have gotten a new view of cancer cells. The work could shed light on the transforming physical properties of these cells as they metastasize, said Jack R. Staunton, a Ph.D. candidate at Arizona State University in the lab of Prof. Robert Ros, and the lead author of a paper reporting on the topic. Metastasis is a critical step in the progression of cancer. It is when the cancer spreads from one organ or part to another. While much is known about metastasis, it remains ...

For ancient Maya, a hodgepodge of cultural exchanges

2013-04-26

The ancient Maya civilization of Mesoamerica may have developed its unique culture and architecture via contact with many other groups—not just exclusive contact with the Olmec people or on its own, without any outside influences, as researchers have debated. According to a new study, the formal plazas and pyramids at Ceibal, an ancient Maya site in Guatemala, probably arose from broad cultural exchanges that took place across southern Mesoamerica from about 1,000 to 700 BCE. Until now, two theories have dominated the debate concerning the origin of the Maya civilization: ...

Archeologists unearth new information on origins of Maya civilization

2013-04-26

This release is available in Japanese. The Maya civilization is well-known for its elaborate temples, sophisticated writing system, and mathematical and astronomical developments, yet the civilization's origins remain something of a mystery. A new University of Arizona study to be published in the journal Science challenges the two prevailing theories on how the ancient civilization began, suggesting its origins are more complex than previously thought. Anthropologists typically fall into one of two competing camps with regard to the origins of Maya civilization. ...

Whales able to learn from others

2013-04-26

Humpback whales are able to pass on hunting techniques to each other, just as humans do, new research has found. A team of researchers, led by the University of St Andrews, has discovered that a new feeding technique has spread to 40 per cent of a humpback whale population. The findings are published today (Thursday 25 April) by the journal Science. The community of humpback whales off New England, USA, was forced to find new prey after herring stocks – their preferred food - crashed in the early 1980s. The solution the whales devised – hitting the water with ...

Culture vultures

2013-04-26

Human tendency to adopt the behaviour of others when on their home territory has been found in non-human primates. Researchers at the University of St Andrews observed 'striking' fickleness in male monkeys, when it comes to copying the behaviour of others in new groups. The study has been hailed by leading primate experts as rare experimental proof of 'cultural transmission' in wild primates to date. The findings could help explain the evolution of our human desire to seek out 'local knowledge' when visiting a new place or culture. The new discovery was made by ...