The Work of Titin Protein Folding as a Major Driver in Muscle Contraction.

The Work of Titin Protein Folding as a Major Driver in Muscle Contraction.
Annu Rev Physiol. 2018 Feb 10;80:327-351
Authors: Eckels EC, Tapia-Rojo R, Rivas-Pardo JA, Fernández JM
Abstract
Single-molecule atomic force microscopy and magnetic tweezers experiments have demonstrated that titin immunoglobulin (Ig) domains are capable of folding against a pulling force, generating mechanical work that exceeds that produced by a myosin motor. We hypothesize that upon muscle activation, formation of actomyosin cross bridges reduces the force on titin, causing entropic recoil of the titin polymer and triggering the folding of the titin Ig domains. In the physiological force range of 4-15 pN under which titin operates in muscle, the folding contraction of a single Ig domain can generate 200% of the work of entropic recoil and occurs at forces that exceed the maximum stalling force of single myosin motors. Thus, titin operates like a mechanical battery, storing elastic energy efficiently by unfolding Ig domains and delivering the charge back by folding when the motors are activated during a contraction. We advance the hypothesis that titin folding and myosin activation act as inextricable partners during muscle contraction.
PMID: 29433413 [PubMed - in process]

Source: Annual Review of Physiology - February 10, 2018 Category: Physiology Authors: Eckels EC, Tapia-Rojo R, Rivas-Pardo JA, Fernández JM Tags: Annu Rev Physiol Source Type: research