biostudies-literatureLee LANIDCD NIH HHSNHLBI NIH HHSHorizon 2020National Institutes of HealthEuropean CommissionNIGMS NIH HHS104631https://www.ebi.ac.uk/biostudies/studies/S-EPMC10141508biostudies-literatureUnknown299(5)For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied their effects on motor activity and structural and assembly properties, respectively. The D515N mutation The Journal of biological chemistryDistinct effects of two hearing loss-associated mutations in the sarcomeric myosin MYH7b.PMC10141508F31DC017927F32 HL152543777204R01 HL141086F31 DC017927R01HL141086R01 GM029090R01GM029090Buvoli AELee LAStump WTGeeves MGreenberg MJBarrick SKWalklate JLeinwand LAfalseDistinct effects of two hearing loss-associated mutations in the sarcomeric myosin MYH7b.For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied their effects on motor activity and structural and assembly properties, respectively. The D515N mutation 2023-01-01T00:00:00Z2023 May2026-04-30T12:29:53.565Z2025-04-04T20:51:11.824ZS-EPMC101415083696349410.1016/j.jbc.2023.104631