Evolutionary conservation in the DNA-binding and -bending properties of HMG-boxes from SRY proteins of primates

Gene. 1995 Mar 10;154(2):277-80. doi: 10.1016/0378-1119(94)00853-k.


Mammalian sex determination is caused by the Y-chromosome gene SRY, which encodes a protein containing a DNA-binding domain (HMG-box) of about 70 amino acids (aa). The HMG-box is very conserved in a wide variety of mammals; conversely, the flanking non-box regions show a high degree of aa sequence divergence, even between closely related species. The HMG-box of human SRY binds sequence-specifically to linear DNA and produces a sharp bend; it also interacts with high affinity to kinked DNA structures irrespective of their sequences. Point mutations associated with sex reversal in XY human females fall within the HMG-box and either affect the affinity for DNA or modify the geometry of the DNA-protein complex. Here, we show that the DNA-binding and -bending properties of the HMG-boxes of SRY from human and seven different primates are extremely similar to each other. Together with other data, this suggests that the inability of mouse and human SRY to substitute for each other is due to differences in the conserved HMG-box, rather than the non-conserved flanking sequences.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Conserved Sequence*
  • DNA Primers
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disorders of Sex Development
  • High Mobility Group Proteins / chemistry
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Phylogeny
  • Point Mutation
  • Primates / genetics*
  • Protein Binding
  • Protein Conformation
  • Sex Determination Analysis
  • Sex Differentiation / genetics*
  • Sex-Determining Region Y Protein
  • Species Specificity
  • Transcription Factors*
  • Y Chromosome


  • DNA Primers
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nuclear Proteins
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • Sry protein, mouse
  • Transcription Factors