Molecular basis of human 46X, Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex

MH Werner, JR Huth, AM Gronenborn, GM Clore - Cell, 1995 - cell.com
MH Werner, JR Huth, AM Gronenborn, GM Clore
Cell, 1995cell.com
The solution structure of the specific complex between the high mobility group (HMG)
domain of SRY (hSRY-HMG), the protein encoded by the human testis-determining gene,
and its DNA target site in the promoter of the M~ illerian inhibitory substance gene has been
determined by multidimensional NMR spectroscopy, hSRY-HMG has a twisted L shape that
presents a concave surface (made up of three helices and the N-and C-terminal strands) to
the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site …
Summary
The solution structure of the specific complex between the high mobility group (HMG) domain of SRY (hSRY-HMG), the protein encoded by the human testis-determining gene, and its DNA target site in the promoter of the M~ illerian inhibitory substance gene has been determined by multidimensional NMR spectroscopy, hSRY-HMG has a twisted L shape that presents a concave surface (made up of three helices and the N-and C-terminal strands) to the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site occurs exclusively in the minor groove and induces a large conformational change in the DNA. The DNA in the complex has an overall 70-80 bend and is helically unwound relative to classical A-and B-DNA. The structure of the complex reveals the origin of sequence-specific binding within the HMG-1/HMG-2 family and provides a framework for understanding the effects of point mutations that cause 46X, Y sex reversal at the atomic level.
cell.com