Towards a molecular understanding of the elasticity of titin.
Vertebrate striated muscle behaves elastically when stretched and this property is thought to reside primarily within the giant filamentous protein, titin (connectin). The elastic portion of titin comprises two distinct structural motifs, immunoglobulin (Ig) domains and the PEVK titin, which is a novel motif family rich in proline, glutamate, valine and lysine residues. The respective contributions of the titin Ig and the PEVK sequences to the elastic properties of the molecule have been unknown so far. We have measured both the passive tension in single, isolated myofibrils from cardiac and skeletal muscle and the stretch-induced translational movement of I-band titin antibody epitopes following immunofluorescent labelling of sites adjacent to the PEVK and Ig domain regions. We found that with myofibril stretch, I-band titin does not extend homogeneously. The Ig domain region lengthened predominantly during small stretch, but such lengthening did not result in measurable passive tension and might be explained by straightening, rather than by unfolding, of the Ig repeats. At moderate to extreme stretch, the main extensible region was found to be the PEVK segment whose unravelling was correlated with a steady passive tension increase. In turn, PEVK domain transition from a linearly extended to a folded state appears to be principally responsible for the elasticity of muscle fibers. Thus, the length of the PEVK sequence may determine the tissue-specificity of muscle stiffness, whereas the expression of different Ig domain motif lengths may set the characteristic slack sarcomere length of a muscle type.
Linke
W A
WA
Institute of Physiology II, University of Heidelberg, Germany.
Ivemeyer
M
M
Olivieri
N
N
Kolmerer
B
B
Rüegg
J C
JC
Labeit
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D064211:Connectin; D004548:Elasticity; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007136:Immunoglobulins; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000502:physiology; D009206:Myocardium / Q000737:chemistry; D009210:Myofibrils / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D051381:Rats; D012518:Sarcomeres / Q000378:metabolism
D000906:Antibodies; D064211:Connectin; D000939:Epitopes; D007136:Immunoglobulins; D009124:Muscle Proteins; D011494:Protein Kinases