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✅   Engineered HMGB1 Construct with Tandem HMG B Domains that Promotes Tissue Regeneration without Potential for Deleterious Inflammation or Thrombosis

science

High Mobility Group Box 1 protein in its fully-reduced state (FR-HMGB1) binds to CXC Ligand 12 (CXCL12) and signals through CXC Receptor 4 (CXCR4) to transition stem and progenitor cells from the quiescent G0 state to GAlert. On exposure to tissue activating factors, cells in GAlert readily enter G1 to effect tissue repair. However, conversion of FR-HMGB1 to the disulfide form may result in deleterious inflammation through signaling via Toll-Like Receptors 2 (TLR-2) and 4 (TLR-4), and the Receptor for Advanced Glycation End products (RAGE). Using peptide arrays, biolayer interferometry and nuclear magnetic resonance, we mapped the residues and motifs of HMGB1 that interact with CXCL12, TLR-2, TLR-4, and RAGE.

BioRxiv     Nov 08, 2024