DNA Binding

A sex-determining interaction

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Science  26 Jun 2015:
Vol. 348, Issue 6242, pp. 1441
DOI: 10.1126/science.348.6242.1441-b

Across much of the animal kingdom, DMRT proteins are involved in regulating sexual development. In humans, DMRT1 both activates a male sex-determining gene and deactivates female sex-determining genes. Murphy et al. report a crystal structure showing three DNA binding DM domains, each comprising a zinc binding module followed by a recognition helix, bound to target DNA. Recognition helices from two domains lie antiparallel in a widened major groove. They find that DMRT1 can bind as a dimer, trimer, or tetramer in vitro and in vivo, with DNA sequence and shape dictating the binding mode. A mutation that causes male-to female sex reversal in humans reduces binding affinity and interferes with the binding stoichiometry of wild-type DMRT1.

Nat. Struct. Mol. Biol. 22, 442 (2015).

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