A Model of Cross-Bridge Attachment to Actin in the A·M·ATP State Based on X-Ray Diffraction from Permeabilized Rabbit Psoas Muscle

Gu, Jie; Xu, Sengen; Yu, Linda Chia‐Hui

doi:10.1016/s0006-3495(02)75559-8

Cited by 34 publications

(26 citation statements)

References 47 publications

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“…3b, ϪCa ϩϩ ) imply that the myosin head in the ADP⅐AlF 4 -II state is in the closed, pre-power-stroke conformation (33), at least while dissociated from actin or while interacting nonstereospecifically with the inactive actin filament. The much weaker MLLs of the ADP⅐AlF 4 -II state at high Ca 2ϩ do not necessarily indicate a post-power-stroke conformation at high Ca 2ϩ because stereospecific binding (increase in the 1.ALL and 5.9-nm ALL) already weakens the MLLs due to disruption of the myosinbased helical arrangement (30)(31)(32).…”

Section: Resultsmentioning

confidence: 96%

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄

Kraft

Mählmann²,

Mattei³

et al. 2005

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

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Motile forces in muscle are generated by the so-called ''power stroke,'' a series of structural changes in the actomyosin crossbridge driven by hydrolysis of ATP. The initiation of this power stroke is closely related to phosphate release after ATP cleavage and to the change of the myosin head from weak, nonstereospecific actin attachment to strong, stereospecific binding. The exact sequence of events, however, is highly controversial but crucial for the mechanism of how ATP hydrolysis drives structural changes in the head domain of myosins and related NTPases like kinesins and small G proteins. Here, we show that the phosphate analogue AlF4 can form two ADP⅐phosphate analog states, one with weak binding of myosin to actin and the other with strong binding of myosin to actin. Thus, change from weak to strong binding (i.e., the initiation of the power stroke) can occur before phosphate is released from the active site.actomyosin cross-bridge ͉ phosphate release ͉ weak binding cross-bridge states ͉ strong binding cross-bridge states ͉ force generation M uscle contraction results from cyclic interactions of the myosin head with actin filaments as ATP is hydrolyzed. Within each cycle, a multistep power stroke drives actin filaments several nanometers past the myosin filaments or generates motile forces when filament sliding is prevented. According to the concept of Lymn and Taylor (1), the power stroke is driven by the release of the ATP-hydrolysis products ADP and phosphate from the active site. From subsequent work, it was proposed that the initiation of the power stroke is closely related to the release of phosphate (2) and to the change of the myosin head from a conformation of weak, nonstereospecific actin binding to a conformation of strong, stereospecific actin attachment (3, 4). The exact sequence of events [i.e., how structural changes in the actomyosin cross-bridge are coupled to changes in actin affinity and to the release of phosphate from the active site] is still unclear. This coupling, however, is crucial for the mechanism of how ATP hydrolysis drives structural changes in the head domain not only of myosins but also of kinesins and small G proteins. Although it is clear that intermediates with MgADP and phosphate in the active site (ADP⅐P i intermediates) are central to the initiation of the power stroke, it is still controversial whether, for example, phosphate release has to occur before the transition to the strong binding conformation (5, 6) or whether a strong binding ADP⅐P i intermediate is formed before phosphate release. A second ADP⅐P i intermediate has been postulated before (7-11), but its properties in terms of weak or strong actin-binding conformation remained unclear. One difficulty in characterizing the ADP⅐P i intermediates is their transient nature during active cross-bridge cycling, specifically of an ADP⅐P i intermediate postulated to bind strongly to actin before the release of phosphate (8-10). To elucidate events around phosphate release, we searched for approaches to accumulate...

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Section: Resultsmentioning

confidence: 96%

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄

Kraft

Mählmann²,

Mattei³

et al. 2005

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

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“…While the position of myosin on the surface of the actin filament in the presence of ATP (weak binding mode) has not been visualized, modeling studies based on the X-ray diffraction from permeabilized muscles suggest that the N-terminus of F-actin is at the interface with the weakly bound myosin head 16 . Our data suggest that the position of myosin in a rigor state would clash with the position of the NTD of SEPT9 in two of its three binding modes (Fig.…”

Section: Resultsmentioning

confidence: 99%

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Smith

Dolat

Angelis

et al. 2015

Journal of Molecular Biology

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Septins are a highly conserved family of proteins in eukaryotes that is recognized as a novel component of the cytoskeleton. Septin 9 (SEPT9) interacts directly with actin filaments and functions as an actin stress fiber cross-linking protein that promotes the maturation of nascent focal adhesions and cell migration. However, the molecular details of how SEPT9 interacts with F-actin remain unknown. Here, we use electron microscopy and image analysis to show that SEPT9 binds to F-actin in a highly polymorphic fashion. We demonstrate that the basic domain (B-domain) of the N-terminal tail of SEPT9 is responsible for actin cross-linking, while the GTP-binding domain (G-domain) does not bundle F-actin. We show that the B-domain of SEPT9 binds to three sites on F-actin, and the two of these sites overlap with the binding regions of myosin and cofilin. SEPT9 inhibits actin-dependent ATPase activity of myosin and competes with the weakly-bound state of myosin for binding to F-actin. At the same time, SEPT9 significantly reduces the extent of F-actin depolymerization by cofilin. Taken together, these data suggest that SEPT9 protects actin filaments from depolymerization by cofilin and myosin, and indicate a mechanism by which SEPT9 could maintain the integrity of growing and contracting actin filaments.

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“…The binding site for C1C2 was localized within the proximal 126 amino acids of S2, 7 ie, the region adjacent to the S1/S2 junction. Because characteristics of the S1/S2 junction, such as its rigidity, mobility, and orientation could all potentially affect the mechanical efficiency of force generation or interactions between S1 heads, 29,30 binding of cMyBP-C to S2 could provide a means for regulating these properties. Similarly, there is evidence that dimerization of the myosin heavy chains may be a dynamic process.…”

Section: Role Of Myosin S2 In the Regulation Of Contractionmentioning

confidence: 99%

Binding of Myosin Binding Protein-C to Myosin Subfragment S2 Affects Contractility Independent of a Tether Mechanism

Harris

Rostkova

Gautel

et al. 2004

Circulation Research

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Abstract-Mutations in the cardiac myosin binding protein-C gene (cMyBP-C) are among the most prevalent causes of inherited hypertrophic cardiomyopathy. Although most cMyBP-C mutations cause reading frameshifts that are predicted to encode truncated peptides, it is not known if or how expression of these peptides causes disease. One possibility is that because the N-terminus contains a unique binding site for the S2 subfragment of myosin, shortened cMyBP-C peptides could directly affect myosin contraction by binding to S2. To test this hypothesis, we compared the effects of a C1C2 protein containing the myosin S2 binding site on contractile properties in permeablized myocytes from wild-type and cMyBP-C knockout mice. In wild-type myocytes, the C1C2 protein reversibly increased myofilament Ca 2ϩ sensitivity of tension, but had no effect on resting tension. Identical results were observed in cMyBP-C knockout myocytes where C1C2 increased Ca 2ϩ sensitivity of tension with the half-maximal response elicited at Ϸ5 mol/L C1C2. Maximum force was not affected by C1C2. However, phosphorylation of C1C2 by cAMP-dependent protein kinase reduced its ability to increase Ca 2ϩ sensitivity. These results demonstrate that binding of the C1C2 peptide to S2 alone is sufficient to affect myosin contractile function and suggest that regulated binding of cMyBP-C to myosin S2 by phosphorylation directly influences myofilament Ca 2ϩ sensitivity.

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A Model of Cross-Bridge Attachment to Actin in the A·M·ATP State Based on X-Ray Diffraction from Permeabilized Rabbit Psoas Muscle

Cited by 34 publications

References 47 publications

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Binding of Myosin Binding Protein-C to Myosin Subfragment S2 Affects Contractility Independent of a Tether Mechanism

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A Model of Cross-Bridge Attachment to Actin in the A·M·ATP State Based on X-Ray Diffraction from Permeabilized Rabbit Psoas Muscle

Cited by 34 publications

References 47 publications

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF 4

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF 4

Septin 9 Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity

Binding of Myosin Binding Protein-C to Myosin Subfragment S2 Affects Contractility Independent of a Tether Mechanism

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Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄

Initiation of the power stroke in muscle: Insights from the phosphate analog AlF ₄