High impact information on HMG-Box Domains

• SRY encodes a protein with a central 'high mobility group' domain (HMG box) of about 78 amino acids [1].
• We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain [2].
• The bending activity was maintained by a 79-amino acid polypeptide corresponding to a single HMG-box domain of HMG1 [3].
• The CP components Cdc68 and Pob3 closely resemble the FACT components, except that the C-terminal high-mobility group (HMG) box domain of SSRP1 is not found in the yeast homolog Pob3 [4].
• Mediated by its C-terminal high mobility group (HMG) box domain, SSRP1 binds DNA non-sequence specifically but recognizes certain DNA structures [5].

Biological context of HMG-Box Domains

• Sequence analysis revealed that this gene had an open reading frame of 538 amino acid residues containing a Sry high-mobility group (HMG) box domain, known as a DNA binding motif, particularly in the Sox family genes [6].
• The HMG box domain is a DNA binding domain present in the nonhistone chromosomal proteins HMG1 and HMG2 and in other proteins involved in the regulation of gene expression [7].
• All the HMG-box domains bind with structure specificity to four-way junctions, but the structure selectivity is significantly greater for A and the SRY box than for the HMG1 B or B' domains, as judged by competition with excess plasmid DNA [8].

Associations of HMG-Box Domains with chemical compounds

• RESULTS: Pauciarticular, but not polyarticular, JRA patient sera were found to recognize a lysine-rich major epitope (KKGKKKDP), which is located in the linker region of the HMG box domains of the HMG-2 nonhistone chromosomal protein [9].
• This interaction is mediated through a specific proline-rich domain in the N-terminal region of Alx4 and requires the DNA-binding domain (HMG-box) of LEF-1 [10].
• Site-directed mutagenesis of intercalating residues in both HMG domains A and B in full-length HMGB1 further supports the conclusion that only one HMG box domain is bound to the site of cisplatin damage [11].
• To examine whether the negative effect of the acidic C-terminal domain is brought about by interactions with the basic part of HMGB1 (N-terminal region, HMG-box domain), intramolecular cross-linking in combination with formic acid cleavage of the protein was used [12].
• Mutational analysis of the HMG1 B-domain revealed that replacement of Lys96 of the extended N-terminal segment (and much less the neighboring Arg97) and Lys128 of helix II to glutamic acid severely impaired binding of the HMG box domain to supercoiled DNA [13].

Gene context of HMG-Box Domains

• Both HMG box domains of HMGB1, A and B, interact with p73alpha [14].
• Whereas L-Sox5 and Sox6 are highly homologous proteins, they are totally different from Sox9 outside the HMG box domain [15].
• The HMG-box domain of the human male sex-determining factor SRY, hSRY(HMG) (comprising residues 57-140 of the full-length sequence), binds DNA sequence-specifically in the minor groove, resulting in substantial DNA bending [16].
• To understand better the basis of this preference, we have studied the binding of HMG1 (which has two tandem HMG boxes linked by a basic extension to a long acidic tail) and Drosophila HMG-D (one HMG box linked by a basic region to a short and less acidic tail), and their HMG-box domains, to 88 bp and 75 bp DNA minicircles [17].
• Among the six HMG box domains in hUBF, the first one can bind to the ribosomal promoter specifically by itself and is essential for the whole protein's DNA binding specificity [18].

Analytical, diagnostic and therapeutic context of HMG-Box Domains

• The interaction of full-length HMGB1, containing two tandem HMG box domains and a C-terminal acidic tail, with cisplatin-modified DNA was investigated by hydroxyl radical footprinting and electrophoretic gel mobility shift assays [11].

References