Featured Research

from universities, journals, and other organizations

Molecular assembly line brings muscles into shape

Date:
January 18, 2013
Source:
Research Institute of Molecular Pathology
Summary:
Scientists have discovered the molecular basis underlying the patterned folding and assembly of muscle proteins.

Cartoon of a molecular assembly line.
Credit: Courtesy of David Greenlees

Scientists at the Research Institute of Molecular Pathology (IMP) in Vienna, Austria and at the University of Cologne, Germany have discovered the molecular basis underlying the patterned folding and assembly of muscle proteins. They describe the strikingly new mechanism in the current issue of Cell.

Muscle development and function rely on the correct assembly of contractile units called the sarcomeres. Their 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.

So far, it has been shown that the folding of myosin involves the assistance of certain molecular chaperones. Chaperones are specialised helper proteins that bring their client proteins into the correct fold and keep them in good shape. The myosin-specific chaperone UNC-45 has been known to play a central role in muscle formation, but its exact function has remained elusive so far.

To address the underlying principle of how myosin filaments are assembled in muscle cells, IMP-Senior Scientist Tim Clausen and PhD-students Linn Gazda and Doris Hellerschmied carried out a detailed biochemical and structural analysis of the UNC-45 protein from the nematode worm C. elegans. Strikingly, their data revealed that UNC-45 can polymerize into a linear protein chain. As a consequence, multiple binding sites for the myosin units as well as for the co-working chaperones are periodically arranged along the UNC-45 chain. Indeed, this multi-chaperone complex precisely mimics an industrial assembly line.

Thorsten Hoppe and Wojciech Pokrzywa from the University of Cologne were able to show that the observed UNC-45 chain also occurs in living cells and is critical for coupling myosin folding with myofilament formation. In C. elegans worms whose UNC-45 protein was defect, the arrangement of muscle filaments was severely disturbed. As a consequence, these worms were paralysed.

The newly discovered mechanism decisively alters the current view of how muscle filaments are formed and, later on, kept in shape. The UNC-45 chaperone represents a novel type of filament assembly factor that provides a molecular scaffold for specific 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 and to what extent this mechanism is connected with protein folding diseases." says Tim Clausen.

Aberrant UNC-45 function is associated with severe muscle defects resulting in skeletal and cardiac myopathies. The new study which is published in the current issue of the journal Cell points to the importance of carefully controlling the level of UNC-45 in order to build-up functional myosin assembly complexes. The discovered mechanism may thus help to develop strategies against diseases connected with myosin assembly defects.


Story Source:

The above story is based on materials provided by Research Institute of Molecular Pathology. Note: Materials may be edited for content and length.


Journal Reference:

  1. Linn Gazda, Wojciech Pokrzywa, Doris Hellerschmied, Thomas Lφwe, Ignasi Fornι, Felix Mueller-Planitz, Thorsten Hoppe, Tim Clausen. The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans. Cell, 2013; 152 (1-2): 183 DOI: 10.1016/j.cell.2012.12.025

Cite This Page:

Research Institute of Molecular Pathology. "Molecular assembly line brings muscles into shape." ScienceDaily. ScienceDaily, 18 January 2013. <www.sciencedaily.com/releases/2013/01/130118064809.htm>.
Research Institute of Molecular Pathology. (2013, January 18). Molecular assembly line brings muscles into shape. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2013/01/130118064809.htm
Research Institute of Molecular Pathology. "Molecular assembly line brings muscles into shape." ScienceDaily. www.sciencedaily.com/releases/2013/01/130118064809.htm (accessed September 19, 2014).

Share This



More Plants & Animals News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) — Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
Powered by NewsLook.com
Chimp Violence Study Renews Debate On Why They Kill

Chimp Violence Study Renews Debate On Why They Kill

Newsy (Sep. 17, 2014) — The study weighs in on a debate over whether chimps are naturally violent or become that way due to human interference in the environment. Video provided by Newsy
Powered by NewsLook.com
Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) — The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) — Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins