Structural evidence for a possible role of reversible disulphide bridge formation in the elasticity of the muscle protein titin

Background: The giant muscle protein titin contributes to the filament syst em in skeletal and cardiac muscle cells by connecting the Z disk and the ce ntral M line of the sarcomere. One of the physiological functions of titin is to act as a passive spring in the sarcomere, which is achieved by the el astic properties of its central I band region. Titin contains about 300 dom ains of which more than half are folded as immunoglobulin-like (Ig) domains . Ig domain segments of the I band of titin have been extensively used as t emplates to investigate the molecular basis of protein elasticity. Results: The structure of the Ig domain II from the I band of titin has bee n determined to 2.1 Angstrom resolution. It reveals a novel, reversible dis ulphide bridge, which is neither required for correct folding nor changes t he chemical stability of ii, but it is predicted to contribute mechanically to the elastic properties of titin in active sarcomeres. From the 92 Ig do mains in the longest isoform of titin, at least 40 domains have a potential for disulphide bridge formation. Conclusions: We propose a model where the formation of disulphide bridges u nder oxidative stress conditions could regulate the elasticity of the I ban d in titin by increasing sarcomeric resistance. In this model, the formatio n of the disulphide bridge could refrain a possible directed motion of the two beta sheets or other mechanically stable entities of the II Ig domain w ith respect to each other when exposed to mechanical forces.