Fig. 4
From: Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism
The unconventional mechanism of force production by PfMyoA. a Overall view of the mechanical communication within the PfMyoA motor domain during the powerstroke. In both the PPS and the Rigor-like states, interactions between Switch-2 and the Wedge are maintained (highlighted by dashed blue lines and detailed in b). The Rigor-like structure indicates that the sequential release of hydrolysis products upon the powerstroke triggers displacement of the Wedge which is associated with straightening of the Relay helix and the converter swing. The PfMyoA unconventional powerstroke requires sequence compensation near the Ser691 (blue dashed lines) since this residue is bulkier than the canonical SH2-SH1Gly found in classical myosins at this position. Thus, motor domain rearrangements are allowed by changes in the interactions between the Wedge and the Relay and SH1-helix connectors (details in b). Additional interactions (highlighted by dashed red lines) involving the N-term extension (purple) also stabilize the Rigor-like state and compensate for the immobility of the SH1-helix. (Details are shown using the same view in c). b Non-conserved residues are highlighted by a red rectangle. The SH1-helix lacks the conserved glycine SH2-SH1Gly at the fulcrum which is replaced by a serine (light pink spheres, S691). A hydrogen bond is formed between S691 and RelayQ494 in both the PPS and Rigor-like states. The presence of a less pliant fulcrum requires sequence adaptation in the Wedge and in the Relay and results in the immobility of the SH1-helix during the powerstroke. Switch-2V475 establishes hydrophobic interactions with SH2H688, helping to stabilize the Rigor-like position of the Switch-2 (red dashed lines). E503 (shown in pink) is a reporter to indicate the kink of the Relay. c In PfMyoA, the converter establishes a network of interactions with the Relay and the SH1-helix. Non-conserved residues are highlighted by a red rectangle. An electrostatic bond between phosphoserine 19 (SEP19) (N-term extension) and K764 (converter), as well as a salt bridge-π interaction between the N-term extensionE6, Switch-1R241, Switch-2F476 (red dashed lines) stabilize the position of the converter in the Rigor-like conformation. For comparison with Myo2, see Supplementary Fig. 5 and Supplementary Movies 2 and 3
