TY - JOUR
T1 - In search of the hair-cell gating spring
T2 - Elastic properties of ankyrin and cadherin repeats
AU - Sotomayor, Marcos
AU - Corey, David P.
AU - Schulten, Klaus
N1 - Funding Information:
This work was partially supported by the National Institutes of Health (NIH P41 RR05969). The authors also acknowledge computer time provided by the National Science Foundation through the National Resource Allocation Committee grant MCA93S028. D.P.C. is an Investigator of the Howard Hughes Medical Institute. We thank P. Michaely for providing us with a model of human ankyrin-R, and members of the Theoretical and Computational Biophysics Group for helpful discussions. We thank Vann Bennett for bringing to our attention the possible elasticity of extended ankyrin repeats. Normal mode analysis (see Supplemental Data ) was performed through the ElNemo web interface ( Suhre and Sanejouand, 2004 ). Plots and curve fits were prepared using xmgrace. The molecular images in this paper were created with the molecular graphics program VMD ( Humphrey et al., 1996 ).
PY - 2005/4
Y1 - 2005/4
N2 - Mechanotransduction in vertebrate hair cells involves a biophysically defined elastic element (the "gating spring") that pulls on the transduction channels. The tip link, a fine filament made of cadherin 23 linking adjacent stereocilia in hair-cell bundles, has been suggested to be the gating spring. However, TRP channels that mediate mechanotransduction in Drosophila, zebrafish, and mice often have cytoplasmic domains containing a large number of ankyrin repeats that are also candidates for the gating spring. We have explored the elastic properties of cadherin and ankyrin repeats through molecular dynamics simulations using crystallographic structures of proteins with one cadherin repeat or 4 and 12 ankyrin repeats, and using models of 17 and 24 ankyrin repeats. The extension and stiffness of large ankyrin-repeat structures were found to match those predicted by the gating-spring model. Our results suggest that ankyrin repeats of TRPA1 and TRPN1 channels serve as the gating spring for mechanotransduction.
AB - Mechanotransduction in vertebrate hair cells involves a biophysically defined elastic element (the "gating spring") that pulls on the transduction channels. The tip link, a fine filament made of cadherin 23 linking adjacent stereocilia in hair-cell bundles, has been suggested to be the gating spring. However, TRP channels that mediate mechanotransduction in Drosophila, zebrafish, and mice often have cytoplasmic domains containing a large number of ankyrin repeats that are also candidates for the gating spring. We have explored the elastic properties of cadherin and ankyrin repeats through molecular dynamics simulations using crystallographic structures of proteins with one cadherin repeat or 4 and 12 ankyrin repeats, and using models of 17 and 24 ankyrin repeats. The extension and stiffness of large ankyrin-repeat structures were found to match those predicted by the gating-spring model. Our results suggest that ankyrin repeats of TRPA1 and TRPN1 channels serve as the gating spring for mechanotransduction.
UR - http://www.scopus.com/inward/record.url?scp=17044401714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17044401714&partnerID=8YFLogxK
U2 - 10.1016/j.str.2005.03.001
DO - 10.1016/j.str.2005.03.001
M3 - Article
C2 - 15837205
AN - SCOPUS:17044401714
SN - 0969-2126
VL - 13
SP - 669
EP - 682
JO - Structure
JF - Structure
IS - 4
ER -