Structural analysis of missense mutations occurring in the DNA-binding domain of HSF4 associated with congenital cataracts.

ABSTRACT: Congenital cataract (CC) is the major cause of childish blindness, and nearly 50% of CCs are hereditary disorders. HSF4, a member of the heat shock transcription factor family, acts as a key regulator of cell growth and differentiation during the development of sensory organs. Missense mutations in the HSF4-encoding gene have been reported to cause CC formation; in particular, those occurring within the DNA-binding domain (DBD) are usually autosomal dominant mutations. To address how the identified mutations lead to HSF4 malfunction by placing adverse impacts on protein structure and DNA-binding specificity and affinity, we determined two high-resolution structures of the wild-type DBD and the K23N mutant of human HSF4, built DNA-binding models, conducted in silico mutations and mol

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC7337047 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature