Data from: Nanomechanics of wild-type and mutant dimers of the tip-link protein protocadherin 15

Mechanical force controls the opening and closing of mechanosensitive ion
channels atop the hair bundles of the inner ear. The filamentous tip link
connecting transduction channels to the tallest neighboring stereocilium
modulates the force transmitted to the channels and thus changes their
probability of opening. Each tip link comprises four molecules: a dimer of
protocadherin 15 and a dimer of cadherin 23, all of
which are stabilized by Ca2+ binding. Using a high-speed optical trap to
examine dimeric PCDH15, we find that the protein's configuration is
sensitive to Ca2+ and that the molecule exhibits limited unfolding at a
physiological Ca2+ concentration. PCDH15 can therefore modulate its
stiffness without undergoing large unfolding events in physiological Ca2+
conditions. The experimentally determined stiffness of PCDH15 accords with
published values for the stiffness of the gating spring, the mechanical
element that controls the opening of mechanotransduction channels. When
PCDH15 has a point mutation, V507D, associated with non-syndromic hearing
loss, unfolding events occur more frequently under tension and refolding
events occur less often than in the wild-type protein. Our results suggest
that the maintenance of appropriate tension in the gating spring is
critical to the appropriate transmission of force to transduction
channels, and hence to hearing.