Disease relevance of TTN

• Small-angle X-ray diffraction experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA and that the lattice spacing is coupled with titin-based passive tension [1].

High impact information on TTN

• The positions of three additional epitopes are compatible with the view that the titin molecule reaches approximately 60 nm into the opposite sarcomere half [2].
• The structure of the sarcomeric M band: localization of defined domains of myomesin, M-protein, and the 250-kD carboxy-terminal region of titin by immunoelectron microscopy [2].
• Mammalian skeletal muscle C-protein: purification from bovine muscle, binding to titin and the characterization of a full-length human cDNA [3].
• Phosphorylation of titin modulates passive stiffness of cardiac muscle in a titin isoform-dependent manner [4].
• To investigate whether or not PKA-induced decreases in passive force result from possible alteration of titin-thin filament interaction (e.g., via troponin I phosphorylation), we conducted the same experiments using RV preparations that had been treated with gelsolin to extract thin filaments [4].

Biological context of TTN

• We conclude that titin affords binding sites to calpain 1, which concentrates the protease in the regions restrained by the Z-band edge and the N1-line as well as at the N2-line level, two sarcomeric regions where early postmortem proteolysis is detected [5].

Anatomical context of TTN

• Titin isoform variance and length dependence of activation in skinned bovine cardiac muscle [1].
• We have explored the role of the giant elastic protein titin in the Frank-Starling mechanism of the heart by measuring the sarcomere length (SL) dependence of activation in skinned cardiac muscles with different titin-based passive stiffness characteristics [1].
• We studied muscle from the bovine left ventricle (BLV), which expresses a high level of a stiff titin isoform, and muscle from the bovine left atrium (BLA), which expresses more compliant titin isoforms [1].
• Immunocytochemical studies using a monoclonal antibody to bovine cardiac titin on intact and extracted myofibrils [6].
• The PKA-induced phosphorylation signals were stronger when myofilaments were first de-phosphorylated by protein phosphatase-1, suggesting inherent phosphorylation of titin in human heart [7].

Associations of TTN with chemical compounds

• The increase was insensitive to the actomyosin inhibitor 2,3-butanedione 2-monoxime, supporting the conclusion that the effect is titin based [8].
• We found that isoprenaline phosphorylated titin and that it reduced diastolic force to a degree similar to that found in skinned RV preparations [4].
• Bovine cardiac titin contained 176 +/- 5 mumol of sulfhydryl groups per gram in the presence of 6 M guanidine hydrochloride or 0.1% SDS; only 45% of these groups were reactive under non-denaturing condition [9].
• 0. These results are consistent with the idea that titin is primarily composed of immunoglobulin C2 and fibronectin type III like motifs throughout its length, including the flexible I band region [9].
• The results showed that there was very little difference in the rate of postmortem degradation of the intact form of titin or of intact nebulin with respect to the two types of samples examined [10].

Other interactions of TTN

• Overall, ES had no detectable effect on titin, nebulin, desmin, or TN-T degradation but accelerated the appearance and enhanced the frequency of three types of I-band fractures in the LM from Bos indicus crossbred cattle [11].

Analytical, diagnostic and therapeutic context of TTN

• Western blot analysis and immunofluorescence studies indicated that N2BA titin expresses E-rich PEVK motifs, whereas they are absent from N2B titin, supporting earlier single molecule studies that reported that E-rich motifs are required for calcium sensitivity [8].
• Circular dichroism measurements indicated that titin contained approximately 53% beta-sheet and 47% random coil at pH 7 [9].
• The SDS-PAGE results showed that the T1 band of titin was absent by 7 d in two animals, by 14 d in four animals, and by 28 d in one animal in both NS and ES samples [11].
• A titin monoclonal antibody (mAb) identified a large family of degradation products that migrated faster than myosin heavy chains and that was more heavily labeled in Western blots of ES samples than in NS samples [12].
• Effect of electrical stimulation on postmortem titin, nebulin, desmin, and troponin-T degradation and ultrastructural changes in bovine longissimus muscle [12].

References