HMGbox

HMG box, short for High Mobility Group box, refers to a small DNA-binding domain of about 80 amino acids found in a broad family of non-histone chromosomal proteins. The best characterized members are the HMGB proteins, which typically contain two HMG-box domains and an acidic C-terminal tail, and function as architectural factors that modulate chromatin structure and gene expression. Other proteins carry a single HMG box, including the sex-determining region Y (SRY) protein and various SOX transcription factors.

Structural features of the HMG box include an L-shaped, three-helix bundle that binds DNA in the minor groove. The domain presents a positively charged surface and recognizes distorted or bent DNA, often bending the double helix to facilitate the assembly of nucleoprotein complexes. Binding is generally less sequence-specific and more structure- or context-dependent, with different boxes showing preferences for particular DNA conformations or damaged DNA.

Functional roles of HMG-box proteins are primarily in the nucleus, where they act as architectural components that promote chromatin remodeling, assist transcription factor cooperation, and participate in DNA repair processes. HMGB proteins, for example, can bend DNA, recruit chromatin remodelers, and influence signaling pathways such as p53. Some HMGB family members can be released extracellularly as alarmins, contributing to immune signaling.

Regulation and evolution of HMG boxes involve post-translational modifications (acetylation, phosphorylation, methylation) that modulate DNA binding, localization, and interactions. The domain is evolutionarily conserved across many eukaryotes, including animals, plants, and fungi, reflecting its essential role in chromatin biology. The discovery and study of HMG boxes have linked chromatin architecture to transcriptional regulation and cellular responses to DNA damage.