Work Done by Titin Protein Folding Assists Muscle Contraction

Fernandez, Julio M.; Kosuri, Pallav; Rivas-Pardo, Jaime Andres; Linke, Wolfgang A.; Popa, Ionel; Eckels, Edward C.


Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin immunoglobulin (Ig) domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single-molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but as yet unrecognized, contributor to the force generated by a contracting muscle.

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Título según WOS: ID WOS:000370190400008 Not found in local WOS DB
Título de la Revista: CELL REPORTS
Volumen: 14
Número: 6
Editorial: Cell Press
Fecha de publicación: 2016
Página de inicio: 1339
Página final: 1347


Notas: ISI