7X2E

Structure of USH1C PDZ2 and coiled-coil in complex with CDHR2 C-terminal tail

Summary for 7X2E

• Entry DOI: 10.2210/pdb7x2e/pdb
• Descriptor: Harmonin, Cadherin-related family member 2, GLYCEROL, ... (4 entities in total)
• Functional Keywords: cell adhesion, peptide binding protein, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 22244.16

Authors

Yan, W.,Chen, G.,Li, J. (deposition date: 2022-02-25, release date: 2022-07-06, Last modification date: 2023-11-29)

Primary citation

Yan, W.,Chen, G.,Li, J.
Structure of the Harmonin PDZ2 and coiled-coil domains in a complex with CDHR2 tail and its implications.
Faseb J., 36:e22425-e22425, 2022

PubMed Abstract: Harmonin is a protein containing multiple PDZ domains and is required for the development and maintenance of hair cell stereocilia and brush border microvilli. Mutations in the USH1C gene can cause Usher syndrome type 1C, a severe inheritable disease characterized by the loss of hearing and vision. Here, by solving the high-resolution crystal structure of Harmonin PDZ2 and coiled-coil domains in a complex with the tail of cadherin-related family member 2, we demonstrated that mutations located in the Harmonin PDZ2 domain and found in patients could affect its stability, and thus, the target binding capability. The structure also implies that the coiled-coil domain could form antiparallel dimers under high concentrations, possibly when Harmonin underwent liquid-liquid phase separation in the upper tip-link density in hair cell stereocilia or microvilli of enterocytes of the intestinal epithelium. The crystal structure, together with the biochemical analysis, provided mechanistic implications for Harmonin mutations causing Usher syndrome, non-syndromic deafness, or enteropathy.

PubMed: 35747925
DOI: 10.1096/fj.202200403RR

Experimental method

X-RAY DIFFRACTION (1.85 Å)