Titin PEVK segment: Charge-driven elasticity of the open and flexible polyampholyte

Muscle Proteomics and Nanotechnology Section, Laboratory of Muscle Biology, NIAMS, NIH, DHHS, Bethesda, MD 20892-8024, USA.
Journal of Muscle Research and Cell Motility (Impact Factor: 2.09). 02/2005; 26(6-8):291-301. DOI: 10.1007/s10974-005-9035-4
Source: PubMed


The giant protein titin spans half of the sarcomere length and anchors the myosin thick filament to the Z-line of skeletal and cardiac muscles. The passive elasticity of muscle at a physiological range of stretch arises primarily from the extension of the PEVK segment, which is a polyampholyte with dense and alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of the human fetal titin PEVK domain (TP1) revealed that when charge interactions were reduced by raising the ionic strength from 35 to 560 mM, its mean persistence length increased from 0.30 +/- 0.04 nm to 0.60 +/- 0.07 nm. In contrast, when the secondary structure of TP1 was altered drastically by the presence of 40 and 80% (v/v) of trifluoroethanol, its force-extension behavior showed no significant shift in the mean persistence length of approximately approximately 0.18 +/- 0.03 nm at the ionic strength of 15 mM. Additionally, the mean persistence length also increased from 0.29 to 0.41 nm with increasing calcium concentration from pCa 5-8 to pCa 3-4. We propose that PEVK is not a simple entropic spring as is commonly assumed, but a highly evolved, gel-like enthalpic spring with its elasticity dominated by the sequence-specific charge interactions. A single polyampholyte chain may be fine-tuned to generate a broad range of molecular elasticity by varying charge pairing schemes and chain configurations.

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Available from: Albert J Jin, Oct 06, 2015
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    • "There are two distinct types of PEVK domains encoded by individual differentiallyspliced exons: Group P exons encode neutral or basic PPAK domains and Group E exons encode acidic polyglutamate-rich domains. The number, specific charge characteristics, and interactions of the domains are important in the overall elasticity of the PEVK segment [Forbes et al., 2005]. Additionally, certain PEVK segments contain SH 3 -binding motifs that may be important for SH 3 -based signaling in the muscle sarcomere [Ma et al., 2006]. "
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