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

Jeffrey G. Forbes, Albert J. Jin, Kan Ma, Gustavo Gutierrez-Cruz, Wanxia L. Tsai, Kuan Wang

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 ∼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.

Original languageEnglish
Pages (from-to)291-301
Number of pages11
JournalJournal of Muscle Research and Cell Motility
Volume26
Issue number6-8
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cell Biology

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