Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How the UNC-45 protein brings muscles into shape

18.01.2013
Insight in the precise arrangement of muscle proteins provides new indications of muscular diseases and cardiac insufficiency

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

Muscle formation and function rely on the correct assembly of myofilaments that are composed of actin and myosin molecules. In a novel study the researchers now discovered the molecular basis underlying the patterned folding and assembly of myosin filaments.

Muscle development and function rely on the correct assembly of contractile units called the sarcomeres. Its main components, thin (actin) and thick (myosin) filaments are organized in a precisely ordered, quasi-crystalline protein framework that mediates muscle contraction. Although the overall architecture of the sarcomere has been studied in detail, little is known about its complicated assembly process. In particular, the mechanism of myosin incorporation into thick filaments is poorly understood.

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.


Publication:
Gazda et al., The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans, Cell (2013), http://dx.doi.org/10.1016/j.cell.2012.12.025

For further Information, please contact:
Prof. Thorsten Hoppe
CECAD Cluster of Excellence at the Universität of Cologne
Zülpicher Straße 47a . 50674 Köln
+ 49 (0) 221-470-1503 . e-mail: thorsten.hoppe@uni-koeln.de

CECAD PR & Marketing, Astrid Bergmeister
+ 49 (0) 221-470-5287 . e-mail: astrid.bergmeister@uk-koeln.de

Astrid Bergmeister | idw
Further information:
http://www.uni-koeln.de
http://dx.doi.org/10.1016/j.cell.2012.12.025

More articles from Life Sciences:

nachricht Subcutaneous Administration of Multispecific Antibody Makes Tumor Treatment Faster & More Tolerable
01.07.2015 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Why human egg cells don't age well
01.07.2015 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Siemens acquires leading UK enforcement provider Zenco Systems

02.07.2015 | Press release

Viaducts with wind turbines, the new renewable energy source

02.07.2015 | Power and Electrical Engineering

NASA sees heavy rain in Tropical Cyclone Chan-Hom

02.07.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>