In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-02-11)
Abstract:
Our muscles contain large numbers of ‘motor proteins’ called myosins. To contract a muscle, many myosin molecules expend energy to ‘walk’ along a filament made from another molecule, called actin, and generate a pulling force. Like other proteins, myosins must fold into the correct shape to work, but high temperatures or other types of stress can disrupt their ability to adopt or maintain the correct shape. Misfolding of myosins, for example, can result in muscular diseases, including those that affect the heart; so there is an ongoing effort to find compounds that can stabilize protein folding and treat these diseases. The small molecule EMD 57033 was discovered over 20 years ago, and its ability to increase the strength of muscle contractions suggested that it could be used to treat chronic heart failure, but the risk of side effects limited its clinical use. The effectiveness of other compounds that improve cardiac muscle function is still routinely compared to EMD 57033, however the exact mechanism responsible for its effect on muscle tissue remained unknown. Now Radke, Taft et al. have identified the part of the myosin protein that EMD 57033 binds to, and shown how this activates muscle contraction. The experiments also, unexpectedly, revealed that EMD 57033 is able to convert misfolded myosin back into the fully functional form. By revealing this refolding effect, the findings of Radtke, Taft et al. suggest that similar small molecules could be used as drugs for the treatment of protein misfolding diseases, muscular diseases, and heart failure.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.01603.001
DOI:
10.7554/eLife.01603.002
DOI:
10.7554/eLife.01603.003
DOI:
10.7554/eLife.01603.004
DOI:
10.7554/eLife.01603.005
DOI:
10.7554/eLife.01603.006
DOI:
10.7554/eLife.01603.007
DOI:
10.7554/eLife.01603.008
DOI:
10.7554/eLife.01603.009
DOI:
10.7554/eLife.01603.010
DOI:
10.7554/eLife.01603.011
DOI:
10.7554/eLife.01603.012
DOI:
10.7554/eLife.01603.013
DOI:
10.7554/eLife.01603.014
DOI:
10.7554/eLife.01603.015
DOI:
10.7554/eLife.01603.016
DOI:
10.7554/eLife.01603.017
DOI:
10.7554/eLife.01603.018
DOI:
10.7554/eLife.01603.019
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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