The cause of diseases such as BSE in cattle and Creutzfeld–Jakob disease in humans is a prion protein. This protein attaches to cell membranes by way of an anchor made of sugar and lipid components (a glycosylphosphatidylinositol, GPI) anchor.
The anchoring of the prions seems to have a strong influence on the transformation of the normal form of the protein into its pathogenic form, which causes scrapie and mad cow disease. A team headed by Christian F. W. Becker at the TU Munich and Peter H. Seeberger at the ETH Zurich has now “recreated” the first GPI-anchored prion in the laboratory. As they report in the journal Angewandte Chemie, they have been able to develop a new general method for the synthesis of anchored proteins.
The isolation of a complete prion protein that includes the anchor has not yet been achieved, nor has it been possible to produce a synthetic GPI-anchored protein. The function of the GPI anchor has thus remained in the dark. A new synthetic technique has now provided an important breakthrough for the German and Swiss team of researchers.
The sugar component of natural prion GPI anchors consists of five sugar building blocks, to which further sugars are attached through branches. Details of the lipid component have not been determined before. As a synthetic target, the researchers thus chose a construct made of the five sugars and one C18-lipid chain and worked out the corresponding synthetic route. First, the anchor was furnished with the sulfur-containing amino acid cysteine. The prion protein was produced with the use of bacteria and was given an additional thioester (a sulfur-containing group). The centerpiece of the new concept is the linkage of the protein and anchor by means of a native chemical ligation, in which the cysteine group reacts with the thioester. This allowed the prion protein to firmly attach to the vesicle membranes by way of the artificial anchor.
This new concept will allow production of sufficient quantities of proteins modified with GPI anchors for in-depth studies. Experiments with the artificial GPI prion protein should help to clarify the influence of membrane association on conversion of the protein into the pathogenic scrapie form. This should finally make it possible to track down the infectious form of the prion.
Author: Christian F. W. Becker, Max-Planck-Institut für molekulare Physiologie, Dortmund (Germany), http://www.ch.tum.de/proteinchemie/
Title: Semisynthesis of a Glycosylphosphatidylinositol-Anchored Prion Protein
Angewandte Chemie International Edition 2008, 47, No. 43, 8215–8219, doi: 10.1002/anie.200802161
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
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...
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...
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...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine