Class I myosins can sense cellular mechanical forces and function as
tension-sensitive anchors or transporters. How mechanical load is transduced
from the membrane-binding tail to the force-generating head in myosin-1 is
unknown. Here we determined the crystal structure of the entire tail of mouse
myosin-1c in complex with apocalmodulin, showing that myosin-1c adopts a stable
monomer conformation suited for force transduction. The lever-arm helix and the
C-terminal extended PH domain of the motor are coupled by a stable post-IQ
domain bound to calmodulin in a highly unusual mode. Ca(2+) binding to
calmodulin induces major conformational changes in both IQ motifs and the
post-IQ domain and increases flexibility of the myosin-1c tail. Our study
provides a structural blueprint for the neck and tail domains of myosin-1 and
expands the target binding modes of the master Ca(2+)-signal regulator
calmodulin.
