Many proteins, the primary building blocks of life, depend on elements such as copper, zinc and other trace elements to function properly. “Some metal molecules are required as a structural component for proteins, while others are used as catalytic cofactors,” explains Ayako Fukunaka, a researcher working with Makoto Hiromura and Shuichi Enomoto at the RIKEN Center for Molecular Imaging Science in Kobe.
Specialized zinc transporter (ZnT) proteins help maintain a steady supply of zinc for various proteins that incorporate this element. Now, new work from this RIKEN team, in collaboration with Taiho Kambe’s group at Kyoto University, has revealed an additional mechanism by which ZnTs contribute to the production of certain zinc-binding proteins.
The enzyme called tissue nonspecific alkaline phosphatase (TNAP) incorporates zinc while undergoing processing in the secretory pathway, a system that subsequently delivers the mature enzyme to the cell membrane. In a series of prior studies, the researchers determined that cells fail to produce stable, functional TNAP in the absence of two particular ZnT complexes. “However, we still did not know whether TNAP degradation results from a decrease in zinc content, lack of ZnT proteins, or both,” says Fukunaka.
To resolve this, she and her colleagues tinkered with cellular expression of ZnT5, ZnT6 and ZnT7, the three proteins that compose these essential zinc-transporting complexes. In the absence of these factors, levels of TNAP dropped dramatically. However, this decrease was only slightly mitigated by treatment with a compound that promotes zinc uptake, suggesting that these proteins also contribute to TNAP production via a second, parallel mechanism.
At an early stage in the secretory pathway, TNAP undergoes chemical modifications that render it resistant to degradation. Fukunaka and her colleagues determined that ZnT complexes appear to facilitate this stabilization. Experiments with mutated versions of these proteins indicated that this stabilization is independent of ZnT-mediated zinc transport, which only becomes important once the immature enzyme has been sufficiently protected against degradation. “We named this phenomenon the elaborate ‘two-step mechanism', in which TNAP protein stabilization by ZnT complexes is followed by conversion of the enzyme to its mature form through the loading of zinc by ZnT complexes,” says Fukunaka.
This dual role for the ZnT proteins is as mysterious as it is surprising, and the researchers are now working to clarify the details of this process and determine whether similar mechanisms are also involved in shepherding other zinc-containing proteins to maturity.
The corresponding author for this highlight is based at the Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging ScienceReference:
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering