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A new method for the purification of myosin long subfragment 2 is presented. This method is based on the fractionation, by DEAE-Sepharose CL-6B ion-exchange chromatography, of either chymotryptic hydrolysates of heavy meromyosin or tryptic hydrolysates of myosin total rod. Although emphasis is given to the purification of long subfragment 2, the method could be easily adapted to the purification of short subfragment 2. 相似文献
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《Cell cycle (Georgetown, Tex.)》2013,12(15):2856-2863
Selection of the cleavage plane during cytokinesis in dividing cells is linked to the position of the mitotic spindle. A major player in cleavage plane positioning is believed to be the anaphase central spindle and its associated signaling complex called centralspindlin, composed of MgcRacGap and MKLP1. Centralspindlin has the capacity to induce furrowing of the cell cortex by promoting the localized activation of RhoA, which in turn promotes assembly of the contractile ring. We have found a way to induce a cytokinesis-like process in unfertilized Drosophila eggs and very early embryos, when spindle structures are few and located far from invaginating egg cortex. The simple injection of a small molecule inhibitor of Cdk1/Cyclin B (either Roscovitin or RO3306) is sufficient to promote membrane invagination near the site of injection. The furrow generated is in many respects similar to a classical cleavage furrow. Actin, myosin, anillin and MKLP1 are all associated with the forming furrow, which in some cases can entirely circumscribe the unfertilized egg. A similar furrow can also be generated by the localized injection of constitutively active RhoA protein, suggesting that Cdk1 is normally an upstream inhibitor of RhoA activation. We show further that this process apparently is not associated with microtubules. Since simple localized inhibition of Cdk1 is sufficient to induce a furrow, we suggest that in real cytokinesis in normal cells, the localized downregulation of Cdk1 activity at the metaphase-anaphase transition may contribute, along with the spindle, to the positioning of the cleavage furrow. 相似文献
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Andrij Baumketner 《Proteins》2012,80(12):2701-2710
Upon ATP binding, myosin motor protein is found in two alternative conformations, prerecovery state M* and postrecovery state M**. The transition from one state to the other, known as the recovery stroke, plays a key role in the myosin functional cycle. Despite much recent research, the microscopic details of this transition remain elusive. A critical step in the recovery stroke is the rotation of the converter domain from “up” position in prerecovery state to “down” position in postrecovery state that leads to the swing of the lever arm attached to it. In this work, we demonstrate that the two rotational states of the converter domain are determined by the interactions within a small structural motif in the force‐generating region of the protein that can be accurately modeled on computers using atomic representation and explicit solvent. Our simulations show that the transition between the two states is controlled by a small helix (SH1) located next to the relay helix and relay loop. A small translation in the position of SH1 away from the relay helix is seen to trigger the transition from “up” state to “down” state. The transition is driven by a cluster of hydrophobic residues I687, F487, and F506 that make significant contributions to the stability of both states. The proposed mechanism agrees well with the available structural and mutational studies. Proteins 2012; © 2012 Wiley Periodicals, Inc. 相似文献
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Tropomyosin (Tpm) is a dimeric coiled-coil protein that binds to filamentous actin, and regulates actin-myosin interaction by moving between three positions corresponding to the blocked, closed, and open states. To elucidate how Tpm undergoes transitions between these functional states, we have built structural models and conducted extensive molecular dynamics simulations of the Tpm-actins/myosin complex in the closed and open states (total simulation time >1.4 μs). Based on the simulation trajectories, we have analyzed the dynamics and energetics of a truncated Tpm interacting with actins/myosin under the physiological conditions. Our simulations have shown distinct dynamics of four Tpm periods (P3-P6), featuring pronounced biased fluctuations of P4 and P5 toward the open position in the closed state, which is consistent with a conformational selection mechanism for Tpm-regulated myosin binding. Additionally, we have identified key residues of Tpm specifically binding to actins/myosin in the closed and open state. Some of them were validated as functionally important in comparison with past functional/clinical studies, and the rest will make promising targets for future mutational experiments. 相似文献
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《Journal of molecular biology》2022,434(23):167872
EF-hand Ca2+-binding proteins (CBPs), such as S100 proteins (S100s) and calmodulin (CaM), are signaling proteins that undergo conformational changes upon increasing intracellular Ca2+. Upon binding Ca2+, S100 proteins and CaM interact with protein targets and induce important biological responses. The Ca2+-binding affinity of CaM and most S100s in the absence of target is weak (CaKD > 1 μM). However, upon effector protein binding, the Ca2+ affinity of these proteins increases via heterotropic allostery (CaKD < 1 μM). Because of the high number and micromolar concentrations of EF-hand CBPs in a cell, at any given time, allostery is required physiologically, allowing for (i) proper Ca2+ homeostasis and (ii) strict maintenance of Ca2+-signaling within a narrow dynamic range of free Ca2+ ion concentrations, [Ca2+]free. In this review, mechanisms of allostery are coalesced into an empirical “binding and functional folding (BFF)” physiological framework. At the molecular level, folding (F), binding and folding (BF), and BFF events include all atoms in the biomolecular complex under study. The BFF framework is introduced with two straightforward BFF types for proteins (type 1, concerted; type 2, stepwise) and considers how homologous and nonhomologous amino acid residues of CBPs and their effector protein(s) evolved to provide allosteric tightening of Ca2+ and simultaneously determine how specific and relatively promiscuous CBP-target complexes form as both are needed for proper cellular function. 相似文献
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