Titin is a giant filamentous protein traversing the half sarcomere of striated muscle with putative functions as diverse as providing structural template, generating elastic response, and sensing and relaying mechanical information. The Z-disk region of titin, which corresponds to the N-terminal end of the molecule, has been thought to be a hot spot for mechanosensing while also serving as anchorage for its sarcomeric attachment. Understanding the mechanics of titin's Z-disk region, particularly under the effect of binding proteins, is of great interest. Here we briefly review recent findings on the structure, molecular associations, and mechanics of titin's Z-disk region. In addition, we report experimental results on the dynamic strength of titin's Z1Z2 domains measured by nanomechanical manipulation of the chemical dimer of a recombinant protein fragment.
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http://dx.doi.org/10.1155/2010/838530 | DOI Listing |
Eur J Neurol
January 2025
Folkhalsan Research Center, Helsinki, Finland.
Background: myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share a common alteration of the sarcomere organization at the level of the Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately muscle degeneration. Most reported cases are due to dominant missense mutations in the MYOT gene, two of which are largely recurrent.
View Article and Find Full Text PDFJ Gen Physiol
January 2025
Chemistry Department, University of Massachusetts Lowell, Lowell, MA, USA.
Titin is the third contractile filament in the sarcomere, and it plays a critical role in sarcomere integrity and both passive and active tension. Unlike the thick and thin filaments, which are polymers of myosin and actin, respectively, titin is a single protein that spans from Z-disk to M-line. The N2A region within titin has been identified as a signaling hub for the muscle and is shown to be involved in multiple interactions.
View Article and Find Full Text PDFElife
December 2024
Translational Cardiology and Functional Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling.
View Article and Find Full Text PDFAnn Clin Transl Neurol
September 2024
Folkhälsan Research Center, Haartmaninkatu 8, 00290, Helsinki, Finland.
Objective: The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy.
View Article and Find Full Text PDFFront Physiol
April 2024
Cellular and Molecular Pathology Program, Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
The giant protein titin is an essential component of muscle sarcomeres. A single titin molecule spans half a sarcomere and mediates diverse functions along its length by virtue of its unique domains. The A-band of titin functions as a molecular blueprint that defines the length of the thick filaments, the I-band constitutes a molecular spring that determines cell-based passive stiffness, and various domains, including the Z-disk, I-band, and M-line, serve as scaffolds for stretch-sensing signaling pathways that mediate mechanotransduction.
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