Ca2+-induced switching of troponin and tropomyosin on actin filaments as revealed by electron cryo-microscopy1 1Edited by A. Klug

Narita, Akihiro; Yasunaga, Takuo; Ishikawa, Takashi; Mayanagi, Kouta; Wakabayashi, T.

doi:10.1006/jmbi.2001.4598

Cited by 108 publications

(107 citation statements)

References 79 publications

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“…Although the torsional rigidity of a coiled coil is probably not high, it would still be difficult for an intact coiled coil to have strictly equivalent interactions with each of seven actin monomers. Analysis of EM reconstructions of thin filaments support a pseudoequivalent interaction (6). At both high and low Ca 2ϩ concentrations, the rotation angle of tropomyosin in the N-terminal half (blocks I-IV) is different from that in the C-terminal half (blocks V-VII) (Fig.…”

Section: Implications For Regulation Of Striated Muscle Contractionmentioning

confidence: 79%

“…The flexibility generated by an alanine cluster (Ala-151, 155, and 158) and nearby Tyr-162 in the coiled-coil core would also help accommodate the difference in the azimuthal position between blocks IV and V. When the alanine cluster (156-162) is replaced, the actin-activated myosin ATPase is suppressed (30). In block I, the EM density corresponding to tropomyosin was too weak to determine the azimuthal position of tropomyosin unambiguously (6). However, the joint-rotation of TM-N at the junction ( Fig.…”

Section: Implications For Regulation Of Striated Muscle Contractionmentioning

confidence: 99%

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Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

Murakami

Stewart

Nozawa

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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103

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-C caused a marked decrease in the affinity of troponin for actin-tropomyosin filaments. The highly conserved region of TnT, in which most cardiomyopathy mutations reside, is crucial for interacting with tropomyosin. The structure of the ternary complex also explains why the skeletal-and cardiac-muscle specific C-terminal region is required to bind TnT and why tropomyosin homodimers bind only a single TnT. On actin filaments, the head-to-tail junction can function as a molecular swivel to accommodate irregularities in the coiled-coil path between successive tropomyosins enabling each to interact equivalently with the actin helix.calcium ͉ cardiomyopathy ͉ troponin

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Section: Implications For Regulation Of Striated Muscle Contractionmentioning

confidence: 79%

Section: Implications For Regulation Of Striated Muscle Contractionmentioning

confidence: 99%

Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

Murakami

Stewart

Nozawa

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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103

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“…Structural information for the intact troponin complex is limited to low-resolution neutron diffraction and electron microscopy studies (11)(12)(13), though several high-resolution structures of TnC with bound TnI peptides are available. Two computational models have been recently proposed for the binary complex of TnC and TnI (14,15).…”

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confidence: 99%

Structure of the inhibitory region of troponin by site directed spin labeling electron paramagnetic resonance

Brown

Sale

Hills

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Site-directed spin labeling EPR (SDSL-EPRtroponin I ͉ spin labels ͉ Fourier transform electron paramagnetic resonance ͉ DEER ͉ dipolar R egulation of striated muscle contraction is associated with Ca 2ϩ -dependent structural transitions in the muscle thin filament, which is composed of the troponin complex, tropomyosin, and actin. Troponin is composed of three components: TnC, which binds Ca 2ϩ ; TnI, which inhibits actomyosin activity; and TnT, which anchors TnC and TnI to tropomyosin. Muscle contraction is initiated by the binding of Ca 2ϩ to the N-lobe regulatory sites of TnC. The N lobe then undergoes a structural transition from a closed to an open form, which then facilitates the release of the inhibitory region of TnI from actin, binding to TnC and stimulation of the actomyosin ATPase. The mechanism of this signaling pathway is still tentative (for review, see ref. 1).Crystal and NMR structures are available for TnC and several complexes of TnC with TnI fragments. The crystal structure of TnC reveals a dumbbell-shaped protein consisting of two globular domains, joined by a 22-residue central ␣-helix (2-4). Each domain contains a hydrophobic cleft and two helix-loop-helix EF-hand metal binding motifs; two high-affinity Ca 2ϩ ͞Mg 2ϩ sites in the C-terminal domain (sites III and IV) and two low-affinity Ca 2ϩ specific sites in the N-terminal domain (sites I and II). In skeletal TnC, sites III and IV are permanently occupied by Mg 2ϩ and facilitate the structural binding of TnC to the contractile apparatus (5). Binding of Ca 2ϩ to sites I and II is the physiological trigger for muscle contraction. In cardiac TnC, binding site I is inactive and Ca 2ϩ binding to site II does not induce as large a structural change as observed in skeletal TnC (6). TnI is capable of inhibiting actomyosin ATPase in the absence of other subunits, but Ca 2ϩ -dependent regulation requires TnC, TnT, and tropomyosin. The inhibitory region (skTnI 96-117) alone can fully inhibit actomyosin ATPase activity (7) possibly by binding either to actin or to TnC in the ''on'' or ''off'' states (8-10). The corresponding residues for the cardiac inhibitory region are 129-150 because of a unique Ϸ32 residue N-terminal extension of cTnI.Structural information for the intact troponin complex is limited to low-resolution neutron diffraction and electron microscopy studies (11-13), though several high-resolution structures of TnC with bound TnI peptides are available. Two computational models have been recently proposed for the binary complex of TnC and TnI (14,15). Both models have TnI and TnC in an antiparallel arrangement with multiple interaction sites between the two subunits. NMR, crystallography, and neutron scattering was used by Tung et al. (15) to develop a computational model of the binary complex in which TnI winds around TnC in either a left-handed manner (model ''L'') or a right-handed manner (model ''R''). In both structures, the inhibitory region of TnI is modeled as a flexible ␤-hairpin in close proximity to the central helix of TnC. ...

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“…The simplest formulation of this model proposes that in high Ca 2ϩ (''on'' position), tropomyosin is located deep in the actin groove, allowing myosin to bind to actin and generate force, whereas in low Ca 2ϩ (''off'' position), tropomyosin is located at higher radius and obstructs the myosin-actin interaction. Although tropomyosin movement also may introduce structural changes in actin and there also may be three states rather than two (15), there is persuasive evidence for the tropomyosin movement itself (16,17). Crick (18) identified the key structural basis for the way the two helices in a coiled-coil interact.…”

mentioning

confidence: 99%

Structural basis for bending tropomyosin around actin in muscle thin filaments

Stewart

2001

Proc. Natl. Acad. Sci. U.S.A.

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Ca2+-induced switching of troponin and tropomyosin on actin filaments as revealed by electron cryo-microscopy1 1Edited by A. Klug

Cited by 108 publications

References 79 publications

Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

Structure of the inhibitory region of troponin by site directed spin labeling electron paramagnetic resonance

Structural basis for bending tropomyosin around actin in muscle thin filaments

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