| Type: | Conserved_site | Name: | HMG-I/HMG-Y, DNA-binding, conserved site |
| Description: | High mobility group (HMG) proteins are a family of relatively low molecular weight non-histone components in chromatin []. HMG-I and HMG-Y (HMGA) are proteins of about 100 amino acid residues which are produced by the alternative splicing of a single gene. HMG-I/Y proteins bind preferentially to the minor groove of AT-rich regions in double-stranded DNA in a non-sequence specific manner [, ]. It is suggested that these proteins could function in nucleosome phasing and in the 3' end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to, AT-rich regions. DNA-binding of these, and several related, proteins is effected by an 11-residue domain known as an AT-hook. Within known HMG-I/Y proteins are found three highly conserved regions, closely related to the consensus sequence TPKRPRGRPKK. A synthetic oligopeptide with this sequence specifically binds to substrate DNA in a manner reminiscent of intact HMG-I/Y proteins. Structure predictions suggest that the peptide has a secondary structure similar to the anti-tumour and anti-viral drugs netropsin and distamycin, and to the dye Hoechst 33258. These ligands, which also preferentially bind to AT-rich DNA, effectively compete with both the synthetic peptide and the HMG-I/Y proteins for DNA binding. The peptide also contains novel structural features such as a predicted Asx bend, or 'hook', at its N terminus, and laterally-projecting cationic Arg/Lys 'bristles', which may play a role in the binding of HMG-I/Y proteins. The predicted peptide structure, the AT-hook, is a previously undescribed DNA-binding motif []. | Short Name: | HMGI/Y_DNA-bd_CS |
