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PDBsum entry 5wjm
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Cell adhesion
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PDB id
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5wjm
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References listed in PDB file
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Key reference
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Title
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Zooming in on cadherin-23: structural diversity and potential mechanisms of inherited deafness.
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Authors
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A.Jaiganesh,
P.De-La-Torre,
A.A.Patel,
D.J.Termine,
F.Velez-Cortes,
C.Chen,
M.Sotomayor.
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Ref.
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Structure, 2018,
26,
1210.
[DOI no: ]
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PubMed id
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Abstract
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Cadherin-23 (CDH23) is an essential component of hair-cell tip links, fine
filaments that mediate inner-ear mechanotransduction. The extracellular domain
of CDH23 forms about three-fourths of the tip link with 27 extracellular
cadherin (EC) repeats that are structurally similar but not identical to each
other. Calcium (Ca2+) coordination at the EC linker regions is key
for tip-link elasticity and function. There are ∼116 sites in CDH23 affected
by deafness-causing mutations, many of which alter conserved
Ca2+-binding residues. Here we present crystal structures showing 18
CDH23 EC repeats, including the most and least conserved, a fragment carrying
disease mutations, and EC repeats with non-canonical Ca2+-binding
motif sequences and unusual secondary structure. Complementary experiments show
deafness mutations' effects on stability and affinity for Ca2+.
Additionally, a model of nine contiguous CDH23 EC repeats reveals helicity and
potential parallel dimerization faces. Overall, our studies provide detailed
structural insight into CDH23 function in mechanotransduction.
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