Transmission of stability information through the N-domain of tropomyosin is interrupted by a stabilizing mutation (A109L) in the hydrophobic core of the stability control region (residues 97-118).

The Journal of Biological Chemistry
J Paul Kirwan, R S Hodges

Abstract

Tropomyosin (Tm) is an actin-binding, thin filament, two-stranded α-helical coiled-coil critical for muscle contraction and cytoskeletal function. We made the first identification of a stability control region (SCR), residues 97-118, in the Tm sequence that controls overall protein stability but is not required for folding. We also showed that the individual α-helical strands of the coiled-coil are stabilized by Leu-110, whereas the hydrophobic core is destabilized in the SCR by Ala residues at three consecutive d positions. Our hypothesis is that the stabilization of the individual α-helices provides an optimum stability and allows functionally beneficial dynamic motion between the α-helices that is critical for the transmission of stabilizing information along the coiled-coil from the SCR. We prepared three recombinant (rat) Tm(1-131) proteins, including the wild type sequence, a destabilizing mutation L110A, and a stabilizing mutation A109L. These proteins were evaluated by circular dichroism (CD) and differential scanning calorimetry. The single mutation L110A destabilizes the entire Tm(1-131) molecule, showing that the effect of this mutation is transmitted 165 Å along the coiled-coil in the N-terminal direction. The singl...Continue Reading

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Dec 27, 2017·The FEBS Journal·Alexander M MatyushenkoDmitrii I Levitsky
Apr 16, 2018·Journal of the Science of Food and Agriculture·Lei FangJun Lu
Oct 5, 2021·Journal of Molecular Biology·Jose K James, Vikas Nanda

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Methods Mentioned

BETA
circular dichroism
targeted mutations
circular
differential scanning calorimetry
Protein Sample

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Origin

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