2LSR

Solution structure of harmonin N terminal domain in complex with a exon68 encoded peptide of cadherin23

Summary for 2LSR

• Entry DOI: 10.2210/pdb2lsr/pdb
• Related: 2KBQ 2KBR
• NMR Information: BMRB: 18441
• Descriptor: Harmonin, peptide from Cadherin-23 (2 entities in total)
• Functional Keywords: protein complex, usher syndrome, structural protein-cell adhesion complex, structural protein/cell adhesion
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 11475.39

Authors

Pan, L.,Wu, L.,Zhang, C.,Zhang, M. (deposition date: 2012-05-04, release date: 2012-08-15, Last modification date: 2024-05-15)

Primary citation

Wu, L.,Pan, L.,Zhang, C.,Zhang, M.
Large protein assemblies formed by multivalent interactions between cadherin23 and harmonin suggest a stable anchorage structure at the tip link of stereocilia.
J.Biol.Chem., 287:33460-33471, 2012

PubMed Abstract: Stereocilia tip links of inner ear hair cells are subjected to constant stretching during hair-bundle deflection, and accordingly are well designed to prevent from being broken by mechanical tensions. The roots of tip links, which couple tip links with the cytoskeleton, supposedly play important roles in withstanding large forces under stimulated conditions. The upper root of the tip link is mainly formed by the cytoplasmic tail of cadherin23 and its actin-anchoring protein harmonin. However, the detailed organization mode of the two proteins that gives rise to a strong upper root remains unclear. Here we show that the exon68-encoded peptide of cadherin23 can either interact with the N-terminal domain (NTD) of harmonin or form a homodimer. We demonstrate that the three harmonin binding sites of cadherin23, namely the NTD-binding motif, the exon68 peptide, and the C-terminal PDZ binding motif, do not synergize with each other in binding to harmonin, instead they facilitate formation of polymeric cadherin23/harmonin complexes. The exon68 peptide can promote the cadherin23/harmonin polymer formation via either binding to harmonin NTD or self-dimerization. We propose that the polymeric cadherin23/harmonin complex formed beneath the upper tip link membranes may serve as part of the stable rootlet structure for anchoring the tip links of stereocilia.

PubMed: 22879593
DOI: 10.1074/jbc.M112.378505

Experimental method

SOLUTION NMR