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Updated: Jun 24, 2026
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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23
1Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
Summary
Harmonin, a key protein in Usher syndrome, binds cadherin 23. Structural studies reveal how harmonin’s N-domain and PDZ domains interact with cadherin 23, explaining Usher interactome assembly.
Area of Science:
- Molecular Biology
- Structural Biology
- Genetics
Background:
- Usher syndrome (USH) is a hereditary disorder causing hearing and vision loss.
- USH results from defects in proteins forming the Usher interactome.
- Harmonin (Ush1C) acts as a central scaffold protein in Usher complex assembly.
Purpose of the Study:
- To elucidate the biochemical and structural mechanisms of Usher protein complex formation.
- To investigate the interaction between harmonin and cadherin 23.
Main Methods:
- Protein domain analysis
- X-ray crystallography
- Biochemical binding assays
Main Results:
- The N-terminal domain of harmonin is autonomously folded and binds a cadherin 23 peptide.
- Crystal structures revealed the binding mechanism between harmonin's N-domain and cadherin 23.
- Harmonin's PDZ domains also bind cadherin 23, elucidated by crystal structures.
Conclusions:
- A multidentate binding mode between harmonin and cadherin 23 was identified.
- This interaction provides a structural basis for Usher complex assembly in auditory hair cells.
- Understanding these interactions is crucial for Usher syndrome research.
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