" Titin " is a term used to describe a pair of closely related megadalton polypeptides that together are the third most abundant myofibrillar protein in a wide range of striated muscles. It has been proposed that titin and another giant protein, nebulin , are the major components of an elastic cytoskeletal lattice within the sarcomere. We have now purified the leading band, titin -2 (T2), of th...

Titin is a giant structural protein in muscle that spans the half sarcomere from the z-line to the M-band. Although much is known about titin’s mechanical properties from tests on isolated molecules or recombinant fragments, there is little information on its behaviour within the structural confines of a sarcomere. Because of its size (>3MDa) and instability, it is hard to isolate titin and tes...

We show that myofibrils of insect flight and leg muscle contain a doublet of polypeptides with apparent molecular weights of 700K (K = 10(3) Mr) (Hmp I) and 600K (Hmp II), respectively. In Locusta migratoria high ionic strength extraction solubilizes only Hmp II, which is readily purified in native form. It probably reflects a proteolytic derivative of the non-extractable Hmp I. On the basis of...

BACKGROUND The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes depend on changes in extracellular matrix fibrillar collagen and cardiomyocyte titin. METHODS AND RESULTS Seventy patients undergoing coronary artery bypass grafting under...

Titin constitutes the third myofilament of cardiac muscle, with a single giant polypeptide spanning from the Z disk to the M-band region of the sarcomere1 (Figure 1). The 1.0-MDa region in the I band is extensible and consists of tandemly arranged immunoglobulin-like domains that make up proximal (near the Z disk) and distal (near the A-I junction) segments, interspersed by the PEVK sequence (r...

Titin is a gigantic filamentous protein of the muscle sarcomere that plays roles in myofibril mechanics and homoeostasis. 3D-structures of multi-domain fragments of titin are now available that start revealing the molecular mechanisms governing its mechanical and scaffolding functions. This knowledge is now being translated into the fabrication of self-assembling biopolymers. Here we review the...

Titin, the third myofilament type of cardiac muscle, contains a molecular spring segment that gives rise to passive forces in stretched myocardium and to restoring forces in shortened myocardium. We studied cardiac titin isoforms (N2B and N2BA) that contain length variants of the molecular spring segment. We investigated how coexpression of isoforms takes place at the level of the half-sarcomer...

Titin is a giant sarcomeric protein that functions as a complex, molecular spring. Its presence in the sarcomere of striated muscle was recognized in the 1980s,1 but its functions have been appreciated only over the past decade, in considerable measure because of the efforts of Granzier, Labeit, Linke, and coworkers.2–4 Earlier work by these investigators and others4 delineated the spring prope...

In This Issue In This Issue Clash of the titin he sarcomere is more than a complicated piece of structural machinery. According to new results by McElhinny et al. (page 125), a building block of striated muscle cells called MURF-1 may also indirectly regulate gene expression. MURF-1 localizes to sarcomeres thanks to its interaction with titin, a major structural component of the muscle sarcomer...

Our initial attempts to immunolabel intact myocardial walls of 4-12 somite stage chick embryos were hindered by the presence of the cardiac jelly that covers the inner myocardial wall surface and prevents the access of antibodies to that surface. We overcame this difficulty by treating the specimens with hyaluronidase, which made the cardiac jelly permeable to the antibodies. An additional noni...