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The Use of SPR to Probe HMGB1 Binding Interactions with Cell Clearance Molecules

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High Mobility Group Box 1 (HMGB1) is a small protein found primarily in the nucleus of eukaryotes. HMGB1 is composed of three parts: a-box, b-box and an acidic terminus of glutamic and aspartic acid residues. Beyond its role in DNA transcription, HMGB1 is characterized by its activity as a proinflammatory cytokine. In damaged or infected cells, HMGB1 will relocate to the extracellular matrix (ECM), where it selectively binds to immune receptors. The two most common HMGB1 receptors are Receptor for Advanced Glycation Endproducts (RAGE) and Toll-like Receptors (TLRs). HMBG1 binding to RAGE and TLRs facilitates innate immune and proinflammatory responses. Ideally, HMGB1 would operate in the ECM to expunge infectious pathogens. However, this does not seem to always be the case. Studies show that the presence of HMGB1 in the ECM has been associated with diseases associated with defective cell clearance, such as lupus and cystic fibrosis. There are four classes of cell clearance molecules in our bodies: eat me signals, find me signals, phagocyte receptors, and adaptor molecules/opsonins. It is unknown how HMGB1 and these classes of cell clearance molecules coordinately interact in patients with such diseases.

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The Use of SPR to Probe HMGB1 Binding Interactions with Cell Clearance Molecules

High Mobility Group Box 1 (HMGB1) is a small protein found primarily in the nucleus of eukaryotes. HMGB1 is composed of three parts: a-box, b-box and an acidic terminus of glutamic and aspartic acid residues. Beyond its role in DNA transcription, HMGB1 is characterized by its activity as a proinflammatory cytokine. In damaged or infected cells, HMGB1 will relocate to the extracellular matrix (ECM), where it selectively binds to immune receptors. The two most common HMGB1 receptors are Receptor for Advanced Glycation Endproducts (RAGE) and Toll-like Receptors (TLRs). HMBG1 binding to RAGE and TLRs facilitates innate immune and proinflammatory responses. Ideally, HMGB1 would operate in the ECM to expunge infectious pathogens. However, this does not seem to always be the case. Studies show that the presence of HMGB1 in the ECM has been associated with diseases associated with defective cell clearance, such as lupus and cystic fibrosis. There are four classes of cell clearance molecules in our bodies: eat me signals, find me signals, phagocyte receptors, and adaptor molecules/opsonins. It is unknown how HMGB1 and these classes of cell clearance molecules coordinately interact in patients with such diseases.