Key result
Calcium causes a major rearrangement of bound calmodulins, dissociation of calmodulin bound to IQ motif 2, and propagated changes in the motor domain of myosin V.
May inform myosin motor studies; leaves open relevance to cardiac myosins in vivo.
The long neck of unconventional myosin V is composed of six tandem "IQ motifs," which are fully occupied by calmodulin (CaM) in the absence of calcium. Calcium regulates the activity, the folded-to-extended conformational transition, and the processive run length of myosin V, and thus, it is important to understand how calcium affects CaM binding to the IQ motifs. Here we used electron cryomicroscopy together with computer-based docking of crystal structures into three-dimensional reconstructions of actin decorated with a motor domain-two IQ complex to provide an atomic model of myosin V in the presence of calcium. Calcium causes a major rearrangement of the bound CaMs, dissociation of CaM bound to IQ motif 2, and propagated changes in the motor domain. Tryptophan fluorescence spectroscopy showed that calcium-CaM binds to IQ motifs 1, 3, and 5 in a different conformation than apoCaM. Proteolytic cleavage was consistent with CaM preferentially dissociating from the second IQ motif. The enzymatic and mechanical functions of myosin V can, therefore, be modulated both by calcium-dependent conformational changes of bound CaM as well as by CaM dissociation.
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Trybus et al. (2007) studied this question. Calcium vs. Absence of calcium was evaluated on Conformational changes and dissociation of calmodulin bound to IQ motifs of myosin V. Calcium causes a major rearrangement of bound calmodulins, dissociation of calmodulin bound to IQ motif 2, and propagated changes in the motor domain of myosin V.
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