Reverse engineering of the giant muscle protein titin.
Through the study of single molecules it has become possible to explain the function of many of the complex molecular assemblies found in cells. The protein titin provides muscle with its passive elasticity. Each titin molecule extends over half a sarcomere, and its extensibility has been studied both in situ and at the level of single molecules. These studies suggested that titin is not a simple entropic spring but has a complex structure-dependent elasticity. Here we use protein engineering and single-molecule atomic force microscopy to examine the mechanical components that form the elastic region of human cardiac titin. We show that when these mechanical elements are combined, they explain the macroscopic behaviour of titin in intact muscle. Our studies show the functional reconstitution of a protein from the sum of its parts.
Department of Physiology and Biophysics, Mayo Foundation, Rochester, Minnesota 55905, USA.
Hongbin
H
Li
Wolfgang A
WA
Linke
Andres F
AF
Oberhauser
Mariano
M
Carrion-Vazquez
Jason G
JG
Kerkvliet
Hui
H
Lu
Piotr E
PE
Marszalek
Julio M
JM
Fernandez
D064211:Connectin; D004548:Elasticity; D019277:Entropy; D006801:Humans; D018625:Microscopy, Atomic Force; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D015202:Protein Engineering; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*
D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases