Key result
Rng2CHD strongly inhibited the motility of actin filaments on myosin II in vitro, halving sliding speed at a 1.3% binding ratio and virtually stopping movement at an 11% binding ratio.
Why the study?
Substoichiometric binding of certain actin-binding proteins induces conformational changes in actin filaments, but the functional consequences of such changes remain an open question.
Sparsely bound Rng2CHD induces global structural changes in actin filaments, interfering with force generation by actin-myosin II.
Answers are grounded in this paper and cite their sources.
May disrupt actin-myosin force generation at low binding ratios; leaves open in vivo cardiac effects.
Substoichiometric binding of certain actin-binding proteins induces conformational changes in a disproportionally large number of actin protomers in actin filaments. Here, we report a case in which such conformational changes in actin filaments have profound functional consequences. Rng2 is an IQGAP protein implicated in the assembly and contraction of contractile rings in Schizosaccharomyces pombe . We found that the calponin-homology actin-binding domain of Rng2 (Rng2CHD) strongly inhibits the motility of actin filaments on myosin II in vitro. On skeletal muscle myosin II-coated surfaces, Rng2CHD halved the sliding speed of actin filaments at a binding ratio of 1.3% (=1/77), and virtually stopped movement at a binding ratio of 11% (=1/9). Rng2CHD also inhibited actin movements on Dictyostelium myosin II, but in this case by inducing the detachment of actin filaments from myosin II-coated surfaces. Rng2CHD induced cooperative structural changes of actin filaments accompanied by shortening of the filament helical pitch, and reduced the affinity between actin filaments and subfragment 1 (S1) of muscle myosin II in the presence of ADP. Intriguingly, actin-activated ATPase of S1 was hardly inhibited by Rng2CHD. We suggest that sparsely bound Rng2CHD induces global structural changes of actin filaments and interferes with the force generation by actin-myosin II.
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Hayakawa et al. (2020) studied In vitro actin-myosin interaction. Rng2CHD (calponin-homology actin-binding domain of Rng2) was evaluated on Actin filament sliding speed on skeletal muscle myosin II-coated surfaces. Rng2CHD strongly inhibited the motility of actin filaments on myosin II in vitro, halving sliding speed at a 1.3% binding ratio and virtually stopping movement at an 11% binding ratio.
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