Researchers of CECAD, the Cluster of Excellence at the University of Cologne, Germany, and the Research Institute of Molecular Pathology (IMP) in Vienna, Austria, provide mechanistic insight how muscle assembly is regulated in development and aging.
The present work by Gazda et al demonstrates that UNC-45 establishes a multi-chaperone complex that allows the folding of myosin in a defined array along the thick filament. The cartoon illustrates the “patterned folding” principle, of how UNC-45 composes a protein assembly line that places the chaperone mechanics Hsp70 and Hsp90 (highlighted) at regularly spaced positions to work on the series of motor domains protruding from the myosin filament.
Copyright – please specify: With friendly permission from David Greenlees
The Hoppe lab and others have shown before that the folding of myosin involves the assistance of three molecular chaperones including Hsp70, Hsp90 and a myosin-specific assembly protein called UNC-45. To address the underlying principle of how myosin filaments are formed in muscle cells, Prof. Thorsten Hoppe and his postdoc Wojtek Pokrzywa teamed up with PD Dr. Tim Clausen and his group to perform a detailed structural and physiological analysis of the UNC-45 protein from the soil nematode Caenorhabditis elegans.
The striking findings of this collaboration, published in the scientific journal Cell, revealed that UNC-45 can polymerize into a linear protein chain. As a consequence, multiple binding sites for the myosin substrate as well as for the co-working chaperones Hsp70 and Hsp90 are periodically arranged along the UNC-45 chain. Indeed, this multi-chaperone complex that works on a series of myosin motor domains mimics an industrial assembly line (Fig.1). This mechanism decisively alters the current view of how muscle filaments are formed during development and kept in shape upon aging:(1) The UNC-45 chaperone functions beyond simple nascent protein folding. It represents a novel type of filament assembly factor that provides the molecular scaffold for Hsp70 and Hsp90 chaperones to work at regularly spaced positions on captured client proteins. It will be interesting to see whether this "patterned folding" mechanism is critical for the assembly of other protein filaments.
(2) The Hoppe lab showed before that aberrant UNC-45 function is associated with severe muscle defects resulting in skeletal and cardiac myopathies. Therefore, the discovered mechanism may help to develop strategies against diseases connected with myosin assembly defects.
Rice study decodes genetic circuitry for bacterial spore formation
24.05.2016 | Rice University
How Neural Circuits Implement Natural Vision
24.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.
In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...
Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices
Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.
When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene
In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...
The trend-forward world of display technology relies on innovative materials and novel approaches to steadily advance the visual experience, for example through higher pixel densities, better contrast, larger formats or user-friendler design. Fraunhofer ISC’s newly developed materials for optics and electronics now broaden the application potential of next generation displays. Learn about lower cost-effective wet-chemical printing procedures and the new materials at the Fraunhofer ISC booth # 1021 in North Hall D during the SID International Symposium on Information Display held from 22 to 27 May 2016 at San Francisco’s Moscone Center.
Staphylococcus aureus usually is a formidable bacterial pathogen. Sometimes, however, weakened forms are found in the blood of patients. Researchers of the University of Würzburg have now identified one mutation responsible for that phenomenon.
Staphylococcus aureus is a bacterium that is frequently found on the human skin and in the nose where it usually behaves inconspicuously. However, once inside...
24.05.2016 | Event News
20.05.2016 | Event News
19.05.2016 | Event News
24.05.2016 | Earth Sciences
24.05.2016 | Information Technology
24.05.2016 | Materials Sciences