Myosin B of Plasmodium falciparum (PfMyoB): in silico prediction of its three-dimensional structure and its possible interaction with MTIP

Abstract

The mobility and invasion strategy of Plasmodium falciparum is governed by a protein complex known as the glideosome, which contains an actin-myosin motor. It has been shown that myosin A of the parasite (PfMyoA) is the myosin of the glideosome, and the interaction of PfMyoA with myosin tail domain interacting protein (MTIP) determines its correct location and its ability to function in the complex. Because PfMyoA and myosin B of P. falciparum (PfMyoB) share high sequence identity, are both small proteins without a tail domain, belong to the class XIV myosins, and are expressed in late schizonts and merozoites, we suspect that these myosins may have similar or redundant functions. Therefore, this work examined the structural similarity between PfMyoA and PfMyoB and performed a molecular docking between PfMyoB and MTIP. Three-dimensional (3D) models obtained for PfMyoA and PfMyoB achieved high scores in the structural validation programs used, and their superimposition revealed high structural similarity, supporting the hypothesis of possible similar functions for these two proteins. The 3D interaction models obtained and energy values found suggested that interaction between PfMyoB and MTIP is possible. Given the apparent abundance of PfMyoA relative to PfMyoB in the parasite, we believe that the interaction between PfMyoB and MTIP would only be detectable in specific cellular environments because under normal circumstances, it would be masked by the interaction between PfMyoA and MTIP.

Analysis of Plasmodium falciparum myosin B ATPase activity and structure in complex with the calmodulin-like domain of its light chain MLC-B

“…For MyoB, MLC-B is the only light chain identified and binds the IQ2 motif ( 8 ). In silico predictions and subsequent experimental data have suggested that the MyoA regulatory light chain MTIP can bind to MyoB ( 16 , 17 ). However, there have been no studies on the second MyoA light chain P. falciparum ELC binding to MyoB.…”

“…During invasion, MyoB remains at the apical tip of merozoites and disappears once the process is completed ( 8 ). MyoB does not colocalize with MyoA, and there is no evidence of association with the glideosome protein complex ( 15 ), even though in silico predictions ( 16 ) and subsequent interaction studies ( 17 ) have suggested the possibility of such interactions. MyoB is not essential for parasite survival ( 8 , 15 ), but it has been hypothesized to be involved in erythrocyte invasion ( 7 ).…”

Characterization of Plasmodium falciparum myosin B in complex with the calmodulin-like domain of its light chain MLC-B

“…In silico predictions and subsequent experimental data have suggested that the MyoA regulatory light chain MTIP can bind to MyoB (16, 17). However, there have been no in vitro experimental data on the second MyoA light chain Pf ELC binding to MyoB.…”

Comparison of high throughput RNA sequences between Babesia bigemina and Babesia bovis revealed consistent differential gene expression that is required for the Babesia life cycle in the vertebrate and invertebrate hosts

“…Babesia bigemina actin, myosin A, and GAP45 have high identity with their B. bovis orthologs (63 to 98%) ( Table 8 ). Babesia bigemina myosin B and myosin light chain (MLC) genes were found to be upregulated in blood-stages ( Table 8 ), suggesting that the movement in B. bigemina could be governed by alternative myosin motors, similar to B. divergens and P. falciparum ( Hernández et al., 2017 ; González et al., 2019 ). In the B. bovis RNA-seq, myosin B expression (BBOV_IV012030) was not significantly different between stages ( Ueti et al., 2021 ).…”