PDBsum entry 2whv

Cell adhesion

PDB id

2whv

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Contents

			Protein chain

					208 a.a. *

			Ligands

					GOL

			Metals

					_CA ×4


					__K ×4


					_CL

			Waters ×187

* Residue conservation analysis

PDB id:

2whv

Links

Name:

Cell adhesion

Title:

Crystal structure of mouse cadherin-23 ec1-2 (all cation binding sites occupied by calcium)

Structure:

Cadherin-23. Chain: a. Fragment: ec1-2, residues 24-228. Synonym: otocadherin. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.36Å

R-factor:

0.201

R-free:

0.221

Authors:

M.Sotomayor,W.Weihofen,R.Gaudet,D.P.Corey

Key ref:

M.Sotomayor et al. (2010). Structural determinants of cadherin-23 function in hearing and deafness. Neuron, 66, 85. PubMed id: 20399731

Date:

07-May-09

Release date:

21-Apr-10

PROCHECK

	Headers

	References

Protein chain

Q99PF4 (CAD23_MOUSE) - Cadherin-23 from Mus musculus

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					3354 a.a. 208 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

	Neuron 66:85 (2010)
PubMed id: 20399731

Structural determinants of cadherin-23 function in hearing and deafness.
M.Sotomayor, W.A.Weihofen, R.Gaudet, D.P.Corey.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

23135401

M.Sotomayor, W.A.Weihofen, R.Gaudet, and D.P.Corey (2012).
Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.

Nature, 492, 128-132.

PDB codes:

4apx 4aq8 4aqa 4aqe 4axw

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.