Structure of the Mg2+-loaded C-lobe of cardiac troponin C bound to the N-domain of cardiac troponin I: comparison with the Ca2+-loaded structure

Biochemistry
Natosha FinleyPaul R Rosevear

Abstract

Cardiac troponin C (cTnC) is the Ca(2+)-binding component of the troponin complex and, as such, is the Ca(2+)-dependent switch in muscle contraction. This protein consists of two globular lobes, each containing a pair of EF-hand metal-binding sites, connected by a linker. In the N lobe, Ca(2+)-binding site I is inactive and Ca(2+)-binding site II is primarily responsible for initiation of muscle contraction. The C lobe contains Ca(2+)/Mg(2+)-binding sites III and IV, which bind Mg(2+) with lower affinity and play a structural as well as a secondary role in modulating the Ca(2+) signal. To understand the structural consequences of Ca(2+)/Mg(2+) exchange in the C lobe, we have determined the NMR solution structure of the Mg(2+)-loaded C lobe, cTnC(81-161), in a complex with the N domain of cardiac troponin I, cTnI(33-80), and compared it with a refined Ca(2+)-loaded structure. The overall tertiary structure of the Mg(2+)-loaded C lobe is very similar to that of the refined Ca(2+)-loaded structure as evidenced by the root-mean-square deviation of 0.94 A for all backbone atoms. While metal-dependent conformational changes are minimal, substitution of Mg(2+) for Ca(2+) is characterized by condensation of the C-terminal portion of th...Continue Reading

References

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Citations

May 15, 2009·The Journal of Biological Chemistry·Jose Renato PintoJames D Potter
Nov 15, 2008·The Journal of Biological Chemistry·Congmin LiJames B Ames
Jan 29, 2014·Pflügers Archiv : European journal of physiology·Natosha L Finley, Tzvia I Cuperman
Sep 25, 2014·Biochemical and Biophysical Research Communications·Tzvia I SpringerNatosha L Finley
Jan 22, 2011·Biochemistry·Stephen R MartinAnnalisa Pastore
Feb 12, 2011·Protein Science : a Publication of the Protein Society·Wakana OhashiToshio Yamazaki
Jan 8, 2010·Protein Science : a Publication of the Protein Society·Hao HuangHans J Vogel
Oct 24, 2006·Biophysical Journal·Marie E Cantino, Abraham Quintanilla
May 5, 2011·Biochemical and Biophysical Research Communications·Franklin Fuchs, Zenon Grabarek
Feb 16, 2005·Journal of Muscle Research and Cell Motility·Monica X LiBrian D Sykes
Nov 8, 2005·Journal of Biochemistry·Wakana OhashiHiroshi Hirota
Feb 19, 2013·Journal of Muscle Research and Cell Motility·Franklin Fuchs, Zenon Grabarek
Oct 24, 2008·Biochemistry·David S PearsonMichael A Geeves

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