Troponin regulatory function and dynamics revealed by H/D exchange-mass spectrometry.

The Journal of Biological Chemistry
Devanand Kowlessur, Larry S Tobacman

Abstract

Muscle contraction is tightly regulated by Ca(2+) binding to the thin filament protein troponin. The mechanism of this regulation was investigated by detailed mapping of the dynamic properties of cardiac troponin using amide hydrogen exchange-mass spectrometry. Results were obtained in the presence of either saturation or non-saturation of the regulatory Ca(2+) binding site in the NH(2) domain of subunit TnC. Troponin was found to be highly dynamic, with 60% of amides exchanging H for D within seconds of exposure to D(2)O. In contrast, portions of the TnT-TnI coiled-coil exhibited high protection from exchange, despite 6 h in D(2)O. The data indicate that the most stable portion of the trimeric troponin complex is the coiled-coil. Regulatory site Ca(2+) binding altered dynamic properties (i.e. H/D exchange protection) locally, near the binding site and in the TnI switch helix that attaches to the Ca(2+)-saturated TnC NH(2) domain. More notably, Ca(2+) also altered the dynamic properties of other parts of troponin: the TnI inhibitory peptide region that binds to actin, the TnT-TnI coiled-coil, and the TnC COOH domain that contains the regulatory Ca(2+) sites in many invertebrate as opposed to vertebrate troponins. Mapping of the...Continue Reading

References

Sep 1, 1993·Proteins·Y BaiS W Englander
Jan 1, 1996·Annual Review of Physiology·L S Tobacman
Feb 1, 1997·Journal of Mass Spectrometry : JMS·D L SmithZ Zhang
Jan 8, 1999·Journal of the American Society for Mass Spectrometry·Z Zhang, A G Marshall
Oct 3, 1999·Nature Structural Biology·B M Huyghues-DespointesC N Pace
Jun 24, 2000·The Journal of Biological Chemistry·L S Tobacman, C A Butters
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·S W Englander
Aug 17, 2000·Methods in Enzymology·C B Arrington, A D Robertson
May 4, 2002·Annual Review of Biophysics and Biomolecular Structure·Irene LuqueErnesto Freire
Sep 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Louise J BrownPiotr G Fajer
Nov 1, 2002·The Journal of Biological Chemistry·Ashley Hinkle, Larry S Tobacman
Feb 16, 2005·Annual Review of Physiology·Tomoyoshi Kobayashi, R John Solaro
Mar 9, 2005·Archives of Biochemistry and Biophysics·Teppei DoiTakao Ojima
Mar 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Maia V VinogradovaRobert J Fletterick
Sep 28, 2005·The Journal of Biological Chemistry·David H HeeleyHoward D White
Nov 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yin-Biao SunMalcolm Irving
Apr 21, 2007·Circulation Research·Brandon J BiesiadeckiPieter P de Tombe
Jun 3, 2008·Journal of Molecular Biology·Agnieszka Galińska-RakoczyWilliam Lehman
Mar 12, 2009·Biochemical and Biophysical Research Communications·Fumiko MatsumotoSatoru Fujiwara

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Citations

Jul 30, 2011·Biochemistry·Edward P ManningSteven D Schwartz
Oct 5, 2010·The Journal of Biological Chemistry·Julie Mouannes KozailiLarry S Tobacman
Oct 5, 2010·The Journal of Biological Chemistry·Devanand Kowlessur, Larry S Tobacman
Oct 16, 2012·The Journal of Biological Chemistry·Devanand Kowlessur, Larry S Tobacman
Jan 25, 2011·The Journal of Biological Chemistry·R John Solaro, Tomoyoshi Kobayashi
Jan 19, 2013·Circulation Research·R John SolaroTomoyoshi Kobayashi
Feb 5, 2014·Biochemistry. Biokhimii︠a︡·I A Katrukha
Mar 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Michael R WilliamsSteven D Schwartz
Oct 11, 2016·Frontiers in Physiology·Mayra de A Marques, Guilherme A P de Oliveira
Apr 14, 2016·Biological Chemistry·Insung NaVladimir N Uversky
May 15, 2012·Journal of Molecular Biology·Edward P ManningSteven D Schwartz

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