TY - JOUR
T1 - The Structure of Lethocerus Troponin C
T2 - Insights into the Mechanism of Stretch Activation in Muscles
AU - De Nicola, Gianfelice
AU - Burkart, Christoph
AU - Qiu, Feng
AU - Agianian, Bogos
AU - Labeit, Siegfried
AU - Martin, Stephen
AU - Bullard, Belinda
AU - Pastore, Annalisa
N1 - Funding Information:
The authors are grateful to Dr. Kevin Leonard for support and for making Clustal lineups, to Laura Sutherland (EMBL) for initial yeast two-hybrid assays, to Dr. David Trentham for moral support and encouragement, and to Drs. Mike Anson and Justin Molloy for helpful discussions. B.A. received a Marie Curie fellowship. B.B. acknowledges the EU 6th Framework grant Myores.
PY - 2007/7/18
Y1 - 2007/7/18
N2 - To gain a molecular description of how muscles can be activated by mechanical stretch, we have solved the structure of the calcium-loaded F1 isoform of troponin C (TnC) from Lethocerus and characterized its interactions with troponin I (TnI). We show that the presence of only one calcium cation in the fourth EF hand motif is sufficient to induce an open conformation in the C-terminal lobe of F1 TnC, in contrast with what is observed in vertebrate muscle. This lobe interacts in a calcium-independent way both with the N terminus of TnI and, with lower affinity, with a region of TnI equivalent to the switch and inhibitory peptides of vertebrate muscles. Using both synthetic peptides and recombinant proteins, we show that the N lobe of F1 TnC is not engaged in interactions with TnI, excluding a regulatory role of this domain. These findings provide insights into mechanically stimulated muscle contraction.
AB - To gain a molecular description of how muscles can be activated by mechanical stretch, we have solved the structure of the calcium-loaded F1 isoform of troponin C (TnC) from Lethocerus and characterized its interactions with troponin I (TnI). We show that the presence of only one calcium cation in the fourth EF hand motif is sufficient to induce an open conformation in the C-terminal lobe of F1 TnC, in contrast with what is observed in vertebrate muscle. This lobe interacts in a calcium-independent way both with the N terminus of TnI and, with lower affinity, with a region of TnI equivalent to the switch and inhibitory peptides of vertebrate muscles. Using both synthetic peptides and recombinant proteins, we show that the N lobe of F1 TnC is not engaged in interactions with TnI, excluding a regulatory role of this domain. These findings provide insights into mechanically stimulated muscle contraction.
KW - CELLBIO
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U2 - 10.1016/j.str.2007.05.007
DO - 10.1016/j.str.2007.05.007
M3 - Article
C2 - 17637342
AN - SCOPUS:34447263324
SN - 0969-2126
VL - 15
SP - 813
EP - 824
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 7
ER -