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PDBsum entry 1la0
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Contractile protein
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PDB id
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1la0
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of calcium-Saturated cardiac troponin c bound to cardiac troponin i.
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Authors
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A.Dvoretsky,
E.M.Abusamhadneh,
J.W.Howarth,
P.R.Rosevear.
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Ref.
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J Biol Chem, 2002,
277,
38565-38570.
[DOI no: ]
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PubMed id
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Abstract
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Cardiac troponin C (TnC) is composed of two globular domains connected by a
flexible linker. In solution, linker flexibility results in an ill defined
orientation of the two globular domains relative to one another. We have
previously shown a decrease in linker flexibility in response to cardiac
troponin I (cTnI) binding. To investigate the relative orientation of
calcium-saturated TnC domains when bound to cTnI, (1)H-(15)N residual dipolar
couplings were measured in two different alignment media. Similarity in
alignment tensor orientation for the two TnC domains supports restriction of
domain motion in the presence of cTnI. The relative spatial orientation of TnC
domains bound to TnI was calculated from measured residual dipolar couplings and
long-range distance restraints utilizing a rigid body molecular dynamics
protocol. The relative domain orientation is such that hydrophobic pockets face
each other, forming a latch to constrain separate helical segments of TnI. We
have utilized this structure to successfully explain the observed functional
consequences of linker region deletion mutants. Together, these studies suggest
that, although linker plasticity is important, the ability of TnC to function in
muscle contraction can be correlated with a preferred domain orientation and
interdomain distance.
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Figure 2.
Fig. 2. Surface representation of Ca^2+-saturated cTnC
bound to cTnI. Hydrophobic surface area is shown in yellow. The
cTnI regulatory and N-terminal domain helices are shown in
magenta and blue, respectively. cTnI peptides were modeled using
the structures of cTnC-(1-89) bound to cTnI-(147-163) (Protein
Data Bank code 1MXL) and sTnC bound to sTnI-(1-47) (Protein Data
Bank code 1A2X). Views A and B are related by a 90° rotation.
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Figure 3.
Fig. 3. Surface representations of EF-hand protein-target
interactions. A, the solution structure of cTnC bound to cTnI .
cTnC was found to have bend, azimuth, and twist angles of
70°, 30°, and  29°,
respectively. B, the x-ray structure of sTnC bound to
sTnI-(1-47) (11). The orientation of sTnC domains is defined by
bend, azimuth, and twist angles of 93°, 162°,
and 25°, respectively. C, the crystal structure of four
Ca^2+-loaded sTnC (36). The orientation of sTnC domains is
defined by bend, azimuth, and twist angles of 12°, 94°,
and 3°,
respectively. The N- and C-terminal domains of TnC are shown in
gold and red, respectively. TnI peptides are shown in magenta
and blue. Superposition of TnC C-terminal domains was used to
provide similar orientations. D, the NMR structure of
Ca^2+-bound CaM complexed with the myosin light chain kinase
peptide (37). The orientation of CaM domains is defined by bend,
azimuth, and twist angles of 111°, 95°,
and 68°,
respectively. The N- and C-terminal domains of CaM are shown in
gold and red, respectively. The CaM-bound myosin light chain
kinase peptide is shown in blue. Superposition of the CaM
C-terminal domain and the TnC C-terminal domain was used to
provide similar orientations.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
38565-38570)
copyright 2002.
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