Bioscientists at Heidelberg University have studied the function of certain proteins, known as Argonaute (Ago) proteins, in the process of gene regulation. They sought to understand why only the Ago2 protein is able to target and directly turn off genes in humans, while the closely related Ago3 protein is not.
The puzzle symbolises the four principle domains from which human Argonaute proteins are built.
Pricture Credits: Dirk Grimm
Using a new investigative method, researchers working with Dr. Dirk Grimm were able to identify for the first time two "motifs" of this protein that, when properly combined with an already known protein domain, give Ago2 its gene-silencing capability. The researchers hope that the results will open up new avenues in basic biological and medical research toward artificially induced gene silencing.
With the aid of their special "directed protein evolution" method, the Heidelberg scientists were able to generate a large library of "hybrids" from human Ago2 and its close cousin Ago3. Individual proteins with the characteristics – the phenotype – of Ago2 were isolated from these chimaeras. A comparative bioinformatic analysis of the candidates with the strongest Ago2 phenotype yielded an "astonishing result", according to Dr. Grimm. The researchers from Heidelberg University's "CellNetworks" Cluster of Excellence observed a recurring accumulation of two short motifs in a special domain of the Argonaute protein, the N terminus at the end of the protein.
"This result was unexpected since the prevailing view holds that a completely different and known protein domain called the PIWI domain is solely responsible for the gene-regulating properties of Ago2," explains Dr. Grimm. "We were able to show, however, that only the correct combination of these three protein components gives Ago2 the ability to turn off genes in a special way." Gene silencing is based on what is known as RNA interference. Ago2, also called the slicer, slices the messenger RNA that transports the data stored in the DNA and translates it into proteins.
According to lead author Nina Schürmann, the results of this research provide new insight into Argonaute proteins. The results demonstrate that special Ago functions are not determined by isolated protein domains, but through the complex interaction of multiple activating or inhibiting domains. The researchers now hope that they will be able to generate completely new protein characteristics in future and, as a result, possibly even further improve RNA interference processes, according to Dr. Grimm. To advance the research further, the Heidelberg scientists generated a library of chimaeras of all four human Argonaute proteins as well as developed analysis software that can also benefit other users. In cooperation with Prof. Dr. Robert Russell and Dr. Leonardo Trabuco, likewise researchers in the "CellNetworks" Cluster of Excellence, a structure of human Ago3 could be modelled for the first time.
Dirk Grimm directs the CellNetworks "Virus-Host Interactions" Junior Research Group, which is located in the BioQuant Center of Heidelberg University. The group belongs to Heidelberg University Hospital‘s Department of Infectious Diseases under the direction of Prof. Dr. Hans-Georg Kräusslich and is supported by the Chica and Heinz Schaller Foundation (CHS). The results of the research were published in “Nature Structural & Molecular Biology”.
Marietta Fuhrmann-Koch | idw
Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society
Calcium may play a role in the development of Parkinson's disease
19.02.2018 | University of Cambridge
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
19.02.2018 | Information Technology
19.02.2018 | Ecology, The Environment and Conservation
19.02.2018 | Life Sciences