ArticleProceedings of the National Academy of Sciences of the United States of America2009
Assembling stable hair cell tip link complex via multidentate interactions between harmonin and cadherin 23.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 76 citations in OpenAlex.
- Functional reassessment of extended splice region variants in MYO7A with hearing loss and Usher syndrome.The Journal of pathology · 2026Article
- Disruption ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Liquid-liquid phase separation in hair cell stereocilia development and maintenance.Computational and structural biotechnology journal · 2023Review
- Myosin motors in sensory hair bundle assembly.Current opinion in cell biology · 2022Review
- Review
- Is Location Everything? Regulation of the Endothelial CCM Signaling Complex.Frontiers in cardiovascular medicine · 2022Review
- Usher Syndrome: Genetics of a Human Ciliopathy.International journal of molecular sciences · 2021Review
- The many roles of myosins in filopodia, microvilli and stereocilia.Current biology : CB · 2021Review
- Phylogenetic analysis of Harmonin homology domains.BMC bioinformatics · 2021Article
- Structure and Membrane Targeting of the PDZD7 Harmonin Homology Domain (HHD) Associated With Hearing Loss.Frontiers in cell and developmental biology · 2021Article
- A heterologous in-cell assay for investigating intermicrovillar adhesion complex interactions reveals a novel protrusion length-matching mechanism.The Journal of biological chemistry · 2020Article
- Interaction of protocadherin-15 with the scaffold protein whirlin supports its anchoring of hair-bundle lateral links in cochlear hair cells.Scientific reports · 2020Article
- Evidence of Echolocation in the Common Shrew from Molecular Convergence with Other Echolocating Mammals.Zoological studies · 2020Article
- A Novel CCM2 Gene Mutation Associated With Cerebral Cavernous Malformation.Frontiers in neurology · 2020Article
- Hair-Bundle Links: Genetics as the Gateway to Function.Cold Spring Harbor perspectives in medicine · 2019Review
- Brush border protocadherin CDHR2 promotes the elongation and maximized packing of microvilli in vivo.Molecular biology of the cell · 2019Article
- Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation.Nature communications · 2018Article
- Photoaffinity-engineered protein scaffold for systematically exploring native phosphotyrosine signaling complexes in tumor samples.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Zooming in on Cadherin-23: Structural Diversity and Potential Mechanisms of Inherited Deafness.Structure (London, England : 1993) · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hereditary hearing-vision loss disease Usher syndrome (USH) is caused by defects in several proteins, most of which form an integrated protein network called Usher interactome. Harmonin/Ush1C is a master scaffold in the assembly of the Usher protein complexes, because harmonin is known to bind to every protein in the Usher interactome. However, the biochemical and structural mechanism governing the Usher protein complex formation is largely unclear. Here, we report that the highly-conserved N-terminal fragment of harmonin (N-domain) immediately preceding its PDZ1 adopts an autonomously-folded domain. We discovered that the N-domain specifically binds to a short internal peptide fragment of the cadherin 23 cytoplasmic domain. The structures of the harmonin N-domain alone and in complex with the cadherin 23 internal peptide fragment uncovered the detailed binding mechanism of this interaction between harmonin and cadherin 23. We further elucidated the harmonin PDZ domain-mediated cadherin 23 binding by solving the structure of the second harmonin PDZ domain in complex with the cadherin 23 carboxyl tail. The multidentate binding mode between harmonin and cadherin 23 provides a structural and biochemical basis for the harmonin-mediated assembly of stable tip link complex in the auditory hair cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.