Mammalian testis-determining factor SRY and the enigma of inherited human sex reversal: frustrated induced fit in a bent protein-DNA complex.

ABSTRACT: Mammalian testis-determining factor SRY contains a high mobility group box, a conserved eukaryotic motif of DNA bending. Mutations in SRY cause XY gonadal dysgenesis and somatic sex reversal. Although such mutations usually arise de novo in spermatogenesis, some are inherited and so specify male development in one genetic background (the father) but not another (the daughter). Here, we describe the biophysical properties of a representative inherited mutation, V60L, within the minor wing of the L-shaped domain (box position 5). Although the stability and DNA binding properties of the mutant domain are similar to those of wild type, studies of SRY-induced DNA bending by subnanosecond time-resolved fluorescence resonance energy transfer (FRET) revealed enhanced conformational fluctuations le

SUBMITTER: Phillips NB 

PROVIDER: S-EPMC3196072 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature