Figure 1

Schematic structures of HMGB1, -2, -3 and -4. HMGB1 is a 25-kDa nuclear protein of 215 amino acids. The first methionine is cleaved off posttranslationally. HMGB1 comprises two DNA-binding domains (blue), boxes A and B, and a negatively charged C-terminal tail (red). The green boxes are connecting segments. The critical cysteines are highlighted in yellow. Box A, when isolated from the rest of the molecule, acts as a specific antagonist of HMGB1. HMGB2, HMGB3 and HMGB4 have a similar overall domain organization, but are products of different genes. No alternative protein products from alternative splicing are known.