Key result
Calcium-calmodulin binds myosin-V lever arms with picomolar affinity to form a bridging complex.
Why the study?
The molecular mechanism of Ca(2+)-dependent calmodulin dissociation from the IQ-region of myosin-V lever arms was unclear.
The formation of a 1:1 bridging complex between calmodulin and two adjacent IQ-motifs in myosin-V provides a molecular mechanism for Ca(2+)-dependent calmodulin dissociation and potential regulation of functional motility through lever-arm distortion.
Preclinical only; leaves open whether calmodulin bridging regulates myosin-V motility in vivo or humans.
Ca(2+)-saturated calmodulin binds to double-length IQ lever-arm sequences from murine myosin-V, forming a 1:1 "bridging" complex with very high affinity, (K9d)<10 pM for double motifs, IQ34, IQ45 and IQ56). Such a 1:1 complex involves interaction of one calmodulin (CaM) molecule with two adjacent IQ-motifs, providing a molecular mechanism for the observed Ca(2+)-dependent CaM dissociation from the IQ-region. Structural considerations suggest that formation of the 1:1 complex requires a severe distortion of the lever-arm, potentially regulating functional motility. This would be consistent with a recent report of diverse, irregular shapes of the lever arm of myosin-V induced by the presence of Ca(2+).
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Martin et al. (2004) studied this question. Ca(2+)-saturated calmodulin was evaluated on Binding affinity to double-length IQ lever-arm sequences from murine myosin-V. Ca(2+)-saturated calmodulin binds to double-length IQ lever-arm sequences from murine myosin-V with very high affinity (Kd < 10 pM), forming a 1:1 bridging complex.
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