Key result
The myo2-E1-Sup2 intragenic suppressor mutation reversed actomyosin ring contraction defects in vitro and in vivo by relieving a steric clash in the upper 50 kDa domain of Myo2p.
Structural analysis of Myo2p mutants in fission yeast reveals that relieving a steric clash in the upper 50 kDa domain rescues cytokinesis defects, providing potential insights into myosin motor function relevant to certain cardiomyopathies.
myo2-E1-Sup2 relieves steric hindrance to restore cytokinesis; leaves open whether analogous motor domain mechanisms operate in mammalian cells.
Cytokinesis in many eukaryotes requires a contractile actomyosin ring that is placed at the division site. In fission yeast, which is an attractive organism for the study of cytokinesis, actomyosin ring assembly and contraction requires the myosin II heavy chain Myo2p. Although myo2-E1, a temperature-sensitive mutant defective in the upper 50 kDa domain of Myo2p, has been studied extensively, the molecular basis of the cytokinesis defect is not understood. Here, we isolate myo2-E1-Sup2, an intragenic suppressor that contains the original mutation in myo2-E1 (G345R) and a second mutation in the upper 50 kDa domain (Y297C). Unlike myo2-E1-Sup1, a previously characterized myo2-E1 suppressor, myo2-E1-Sup2 reverses actomyosin ring contraction defects in vitro and in vivo. Structural analysis of available myosin motor domain conformations suggests that a steric clash in myo2-E1, which is caused by the replacement of a glycine with a bulky arginine, is relieved in myo2-E1-Sup2 by mutation of a tyrosine to a smaller cysteine. Our work provides insight into the function of the upper 50 kDa domain of Myo2p, informs a molecular basis for the cytokinesis defect in myo2-E1, and may be relevant to the understanding of certain cardiomyopathies.
No takes yet. Share an insight, caveat, or question.
Palani et al. (2018) studied Cytokinesis defect in fission yeast. myo2-E1-Sup2 intragenic suppressor mutation vs. myo2-E1 mutant was evaluated on Actomyosin ring contraction defects in vitro and in vivo. The myo2-E1-Sup2 intragenic suppressor mutation reversed actomyosin ring contraction defects in vitro and in vivo by relieving a steric clash in the upper 50 kDa domain of Myo2p.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: