Effect of calcium-sensitizing mutations on calcium binding and exchange with troponin C in increasingly complex biochemical systems.

Biochemistry
Svetlana B TikunovaJonathan P Davis

Abstract

The calcium-dependent interactions between troponin C (TnC) and other thin and thick filament proteins play a key role in the regulation of cardiac muscle contraction. Five hydrophobic residues (Phe(20), Val(44), Met(45), Leu(48), and Met(81)) in the regulatory domain of TnC were individually substituted with polar Gln, to examine the effect of these mutations that sensitized isolated TnC to calcium on (1) the calcium binding and exchange with TnC in increasingly complex biochemical systems and (2) the calcium sensitivity of actomyosin ATPase. The hydrophobic residue mutations drastically affected calcium binding and exchange with TnC in increasingly complex biochemical systems, indicating that side chain intra- and intermolecular interactions of these residues play a crucial role in determining how TnC responds to calcium. However, the mutations that sensitized isolated TnC to calcium did not necessarily increase the calcium sensitivity of the troponin (Tn) complex or reconstituted thin filaments with or without myosin S1. Furthermore, the calcium sensitivity of reconstituted thin filaments (in the absence of myosin S1) was a better predictor of the calcium dependence of actomyosin ATPase activity than that of TnC or the Tn co...Continue Reading

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Citations

Apr 19, 2012·The Journal of Biological Chemistry·Bin LiuJonathan P Davis
Mar 22, 2014·Archives of Biochemistry and Biophysics·Nicholas SwindleSvetlana B Tikunova
Sep 25, 2014·Journal of Molecular and Cellular Cardiology·Hussam E SalhiBrandon J Biesiadecki
Feb 24, 2016·Archives of Biochemistry and Biophysics·Jonathan P DavisShane D Walton
Dec 8, 2014·Journal of Molecular and Cellular Cardiology·Sarah E LangMargaret V Westfall
Mar 5, 2013·Archives of Biochemistry and Biophysics·Dan WangMichael Regnier
Nov 3, 2012·Protein Expression and Purification·Michael W Lassalle
Mar 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Michael R WilliamsSteven D Schwartz
Sep 20, 2011·Journal of Molecular and Cellular Cardiology·F S KorteMichael Regnier
Nov 3, 2010·Journal of Molecular and Cellular Cardiology·Kareen L KreutzigerMichael Regnier
Aug 16, 2016·Exercise and Sport Sciences Reviews·Edward P Debold
Jan 10, 2017·Frontiers in Physiology·Jalal K SiddiquiJonathan P Davis
May 24, 2017·The Journal of Biological Chemistry·Charles M StevensGlen F Tibbits
Nov 18, 2018·The Journal of General Physiology·Svetlana B TikunovaJonathan P Davis
Feb 27, 2021·Journal of Molecular and Cellular Cardiology·Srboljub M MijailovichMichael Regnier

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