SAXS studies of the heterocomplex HMGB1-CXCL12: implications for cancer research

The heterocomplex formed by the alarmin HMGB1 (High Mobility Group Box 1) and cytokine CXCL12 is relevant in inflammation related diseases (e.g. cancer) as it promotes C-X-C chemokine receptor type 4 (CXCR4)-dependent recruitment of inflammatory cells to injured tissues and exacerbates the immune response in pathological conditions. This heterocomplex is a fundamental drug-target, however its three-dimensional (3D) structure is still unknown because of the challenges posed by the intrinsic dynamics of the system. To obtain structural information on the heterocomplex assembly in solution we aim to integrate our biophysical data on the complex (obtained by means of NMR, MST, AUC) with SAXS measurements. Molecular details on this heterocomplex will be fundamental for the development of drugs inhibiting this crucial pro-inflammatory complex.