2012
DOI: 10.1074/jbc.m111.281600
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Structural Dynamics of C-domain of Cardiac Troponin I Protein in Reconstituted Thin Filament

Abstract: Background:The kinetics and dynamics of the C-domain of cTnI were studied. Results: Fluorescence anisotropy data show support for the fly casting model and a fourth state of thin filament activation. Conclusion: The fly casting model holds true in the thin filament, but the presence of S1 modulates the process. Significance: Our study provides information on the role of the cTnI C-domain in thin filament regulation.

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Cited by 28 publications
(72 citation statements)
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“…During systole, Ca 2+ binding to the N-domain of cTnC causes a partial exposure of the hydrophobic cleft of the N-domain of cTnC [7, 8], followed by the interaction between the hydrophobic cleft of cTnC and the switch region of cTnI [1, 4, 911]. This latter interaction drags both the inhibitory region and mobile domain of cTnI (cTnI-MD) toward cTnC as they release from actin [7, 8, 10, 1216]. These movements of the C-terminus of cTnI alter the orientation and flexibility of troponin and tropomyosin relative to the actin filament [17], and cause tropomyosin to move on the actin surface from the blocked-state toward the closed-state [18], thereby permitting strong cross-bridge binding with actin [6, 18–22].…”
Section: Introductionmentioning
confidence: 99%
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“…During systole, Ca 2+ binding to the N-domain of cTnC causes a partial exposure of the hydrophobic cleft of the N-domain of cTnC [7, 8], followed by the interaction between the hydrophobic cleft of cTnC and the switch region of cTnI [1, 4, 911]. This latter interaction drags both the inhibitory region and mobile domain of cTnI (cTnI-MD) toward cTnC as they release from actin [7, 8, 10, 1216]. These movements of the C-terminus of cTnI alter the orientation and flexibility of troponin and tropomyosin relative to the actin filament [17], and cause tropomyosin to move on the actin surface from the blocked-state toward the closed-state [18], thereby permitting strong cross-bridge binding with actin [6, 18–22].…”
Section: Introductionmentioning
confidence: 99%
“…The functional importance of cTnI-MD is believed to be associated with the unique structural properties of the region. The cTnI-MD is intrinsically disordered, and undergoes a disordered-ordered structural transition while interacting with actin, allowing the cTnI-MD to perform its fly-casting activity to rapidly initiate the relaxation [16, 5254]. The C-terminal end segment of cTnI-MD (residues 193–210) has been shown to interact with tropomyosin [55] and cTnC [56] in a Ca 2+ -sensitive manner and to help restrict tropomyosin position at diastole.…”
Section: Introductionmentioning
confidence: 99%
“…This changes the conformation for both the inhibitory region (cTnI-Ir) and cTnI-Sr [911] switching cTnI-Ir from interacting with actin to interacting with cTnC [12]. Furthermore, the interaction between the mobile domain of cTnI (cTnI-Md) and actin becomes disrupted [13, 14]. These structural changes in the core domain of cTn are propagated through cTnT to Tm leading to azimuthal movement of Tm on the actin surface [15] which permits strong cross-bridge binding.…”
Section: Introductionmentioning
confidence: 99%
“…This Ca 2+ -sensitizing effect of cTnT(3M) and cTnT(4M) in the Mg 2+ state was correlated with a significant decrease in Mg 2+ -state cTnI-cTnC distances as well as a reduction in "switching distance" (total Ca 2+ -induced change in distance between N-cTnC and cTnI-Sr). Finally, significant effects of cTnT pseudo-phosphorylations on the kinetics of Ca 2+ -dissociation-induced changes in N-cTnC–C-cTnI distances were confined to the structural changes sensed by cTnC(89C DDPM )-cTnI(167C AEDANS ), suggesting a specific kinetic effect of cTnT on the C-terminal portion of the C-domain, particularly the mobile domain of cTnI (cTnI-Md), in response to thin filament deactivation, perhaps indicating a change in the orientation but not the distance between cTnC and cTnI along with a concomitant disruption of the fly casting mechanism [13, 14]. Taken together, these results indicate that T204E reduces the Ca 2+ -sensitivity of cTnI-cTnC switching through subtle structural changes not apparent from cTnI-cTnC distance measurements, whereas additional pseudo-phosphorylations compensated for this Ca 2+ -desensitizing effect in the absence of S1 by promoting increased, Ca 2+ -sensitizing interaction between cTnI-Sr and N-cTnC.…”
Section: Introductionmentioning
confidence: 99%
“…Within this volume the probability of quenching is unity (44). The Stern-Volmer coefficient for each mutant is equal to the slope obtained by fitting the data to a straight line with a y-intercept of 1.…”
Section: With Nbd a 2 MM Stock Solution Of N-((2-(iodoacetoxy)ethyl)mentioning
confidence: 99%