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PDBsum entry 2whv
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Cell adhesion
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PDB id
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2whv
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References listed in PDB file
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Key reference
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Title
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Structural determinants of cadherin-23 function in hearing and deafness.
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Authors
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M.Sotomayor,
W.A.Weihofen,
R.Gaudet,
D.P.Corey.
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Ref.
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Neuron, 2010,
66,
85.
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PubMed id
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Abstract
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The hair-cell tip link, a fine filament directly conveying force to
mechanosensitive transduction channels, is composed of two proteins,
protocadherin-15 and cadherin-23, whose mutation causes deafness. However, their
molecular structure, elasticity, and deafness-related structural defects are
unknown. We present crystal structures of the first and second extracellular
cadherin repeats of cadherin-23. Overall, structures show typical cadherin
folds, but reveal an elongated N terminus that precludes classical cadherin
interactions and contributes to an N-terminal Ca(2+)-binding site. The deafness
mutation D101G, in the linker region between the repeats, causes a slight bend
between repeats and decreases Ca(2+) affinity. Molecular dynamics simulations
suggest that cadherin-23 repeats are stiff and that either removing Ca(2+) or
mutating Ca(2+)-binding residues reduces rigidity and unfolding strength. The
structures define an uncharacterized cadherin family and, with simulations,
suggest mechanisms underlying inherited deafness and how cadherin-23 may bind
with itself and with protocadherin-15 to form the tip link.
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