Adaptations in titin's spring elements in normal and cardiomyopathic hearts.
The giant elastic protein titin contains an extensible segment that underlies the majority of physiological passive muscle stiffness. The extensible segment comprises mechanically distinct and serially-linked spring elements: the tandem Ig segments, the PEVK and the cardiac-specific N2B unique sequence. Under physiological conditions the tandem Ig segments are likely to largely consist of folded Ig domains whereas the N2B unique sequence and PEVK are largely unfolded and behave as wormlike chains with different persistence lengths. The mechanical characteristics of titin's extensible region may be tuned to match changing mechanical demands placed on muscle, using mechanisms that operate at different time scales and that include post-transcriptional and post-translational processes.
Granzier
Henk
H
VCAPP, Washington State University, Pullman, WA 99164-6520, USA.
Labeit
Dietmar
D
Wu
Yiming
Y
Witt
Christian
C
Watanabe
Kaori
K
Lahmers
Sunshine
S
Gotthardt
Michael
M
Labeit
Siegfried
S
D000199:Actins / Q000737:chemistry; D017398:Alternative Splicing; D000818:Animals; D002118:Calcium / Q000737:chemistry; D009202:Cardiomyopathies / Q000473:pathology*; D064211:Connectin; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018625:Microscopy, Atomic Force; D016253:Microscopy, Immunoelectron; D009124:Muscle Proteins / Q000737:chemistry*; D009206:Myocardium / Q000737:chemistry*; D010766:Phosphorylation; D020033:Protein Isoforms; D011494:Protein Kinases / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012518:Sarcomeres / Q000502:physiology
D000199:Actins; D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D011494:Protein Kinases; D002118:Calcium