{'fraction_non_alphanumeric': 0.019198664440734557, 'fraction_numerical': 0.005843071786310518, 'mean_word_length': 5.735955056179775, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Structure of the Harmonin PDZ2 and coiled‐coil domains in a complex with CDHR2 tail and its implications

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.