7ep7 | pdb_00007ep7
The complex structure of Gpsm2 and Whirlin
Structural highlights
DiseaseWHRN_HUMAN Defects in DFNB31 are the cause of deafness autosomal recessive type 31 (DFNB31) [MIM:607084. DFNB31 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[1] [2] [3] Defects in DFNB31 are the cause of Usher syndrome type 2D (USH2D) [MIM:611383. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. FunctionWHRN_HUMAN Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear (By similarity). Publication Abstract from PubMedThe mechanosensory stereocilia in hair cells are organized into rows of graded height, a property crucial for auditory perception. Gpsm2-Galphai-Whirlin-Myo15-Eps8 complex at tips of the tallest stereocilia is proposed to define hair bundle row identity, although the underlying mechanism remains elusive. Here, we find that Gpsm2 could undergo phase separation. Moreover, row 1-specific Gpsm2-Galphai complex significantly promotes the formation of the five-component tip complex density (5xTCD) condensates. The 5xTCD condensates display much stronger actin-bundling ability than those without Gpsm2-Galphai, which may provide critical insights into how Gpsm2-Galphai specifies the tallest stereocilia. A deafness-associated mutation of Gpsm2 leads to impaired formation of the 5xTCD condensates and consequently reduced actin bundling, providing possible clues for etiology of hearing loss in patients with Chudley-McCullough syndrome. Promotion of row 1-specific tip complex condensates by Gpsm2-Galphai provides insights into row identity of the tallest stereocilia.,Shi Y, Lin L, Wang C, Zhu J Sci Adv. 2022 Jun 10;8(23):eabn4556. doi: 10.1126/sciadv.abn4556. Epub 2022 Jun , 10. PMID:35687681[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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