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PDBsum entry 2jnf
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Metal binding protein
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PDB id
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2jnf
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References listed in PDB file
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Key reference
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Title
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The structure of lethocerus troponin c: insights into the mechanism of stretch activation in muscles.
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Authors
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G.De nicola,
C.Burkart,
F.Qiu,
B.Agianian,
S.Labeit,
S.Martin,
B.Bullard,
A.Pastore.
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Ref.
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Structure, 2007,
15,
813-824.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 2.
Figure 2. Conformational Status of the Two Lobes of F1 TnC
(A) Structural comparison of the two lobes of F1 TnC with
the PDB picks up as the highest hits the apo N lobe of skeletal
TnC, which is in closed conformation (PDB code: 1skt; Tsuda et
al., 1999) and the holo C lobe of cardiac TnC in complex with
the corresponding N terminus of TnI (PDB code: 1ozs; Lindhout
and Sykes, 2003).
(B) Comparison of the HSQC spectra of apo
(blue) and holo (red) Lethocerus F1 TnC. The spectra were
recorded at 25°C on a 600 MHz spectrometer. The shift upon
Ca^2+ addition of the resonance of V144 is indicated.
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Figure 6.
Figure 6. Modeling of the Complex
(A) Structural
superposition of the four available structures of TnC complexes
(PDB codes: 1a2x, 1j1d, 1ytz, and 1yv0) with the N terminus of
TnI. The structures were superposed on the C lobe of TnC. The
comparison shows that, despite the differences in the relative
orientation of the N lobe, TnI interacts in the same groove and
adopts the same relative orientation to the C lobe.
(B)
Comparison of the network of interactions formed between the C
lobe of TnC and TnI in the cardiac complex (Takeda et al., 2003)
(left panel) and in a homology model built (right panel) using
the cardiac structure (PDB code: 1j1d) as a template. The side
chains of the key residues involved are displayed explicitly and
labeled in red and green according to whether they correspond to
TnI and TnC, respectively, for the cardiac structure. Similarly,
they are colored in red and blue according to whether they
correspond to Lethocerus TnH and TnC, respectively.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2007,
15,
813-824)
copyright 2007.
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