Figure 4. PfELC binds a degenerate IQ motif.

(a) Sequence alignment of PfMyoA IQ1 to the consensus IQ motif and IQ motifs from other myosins: MyoA from Toxoplasma gondii (TgmyoA); bay scallop (Argopecten irradians) myosin 2 (ScMyo2); human (Homo sapiens) β-cardiac myosin 2 (Cardiac); human smooth muscle myosin 2 (SmMyo2); human myosin 6 (MyoVI). Consensus residues are contoured by a black box. (b) The intra-lobe linker of the scallop C-lobe interacts with the HC consensus residues with polar contacts. (c) In contrast, the intra-lobe linker of the Pf C-lobe is predominantly bound to the HC with apolar contacts. (d,e) Intra-lobe interactions maintain the semi-open C-lobe. Specificity in the recognition of the PfELC occurs via the W777 residue in PfMyoA. (d) In conventional myosins such as ScMyo2, a small side chain (I782) is found at the equivalent position, contributing to few interactions within the semi-open lobe. (e) In PfMyoA the bulky Trp (W777) is sandwiched between the α5*, α5’* and α6 helices, increasing the hydrophobic interactions with the PfELC C-lobe.

Figure 4—figure supplement 1. Interaction between the IQ1 motif and the ELC.

(a) Sequence alignment of the IQ1 motif from ScMyo2 and PfMyoA. Residues interacting with the ELCs are contoured following the same color code as defined in Figure 4. (b, c) Two different orientations (180° rotation around the y axis) are shown to depict all residues involved in the IQ1 motif/ELC complex recognition, in order to compare (b) ScMyo2 and (c) PfMyoA Residues at consensus positions are labeled in red.(d) The tryptophan W777 stabilizes the α5* and α5’* helices. The left and the right panels show W777 and its environment in the structures of PfMyoA•FL-PPS and PfMyoA•FL-PR, respectively. Note the change in position of the W777 side chain due to its position at the kink of the pliant region. In PfMyoA•FL-PPS, W777 interacts with the α5* and α5’* helices stabilizing their structure. In PfMyoA•FL-PR, the interaction between W777 and the α5* and α5’* helices are lost due to the kink at the pliant region, and a loss of interaction of these helices with the Converter. These helices become disordered.

Figure 4—figure supplement 2. The converter/ELC interface differs in PfMyoA and in ScMyo2.

(a) The first IQ motif residues of PfMyoA starts one residue downstream to that of ScMyoA (PDB code 1QVI), resulting in a sequence shift in the pliant region and different orientation for the consensus IQ1 motif residues (balls). A difference in the kink at the pliant region accentuates the difference in position of the IQ1 residues in the two lever arms. (b, c) The C-lobe of PfELC and ScELC bound to the IQ1 motif are shown for comparison. The difference in the position of the HC consensus residues results in a different converter/ELC interface in (b) ScMyo2 compared with (c) PfMyoA (see Figure 6 for details of the interactions).