Suresh Kumar, MSC, PhD

Saint Louis University (SLU)

ß2-Glycoprotein I (ß2GPI) is an abundant plasma protein having phospholipid-binding properties. It is known to be the major target antigen of antiphospholipid antibodies (aPLs) in antiphospholipid syndrome (APS), a life-threatening autoimmune thrombotic disease. Indeed, aPLs prefer membrane-bound ß2GPI to that in solution.
Furthermore, ß2GPI can adopt multiple conformations (i.e. J-elongated, S-twisted, and O-circular). While strong evidence indicates that the J-form is the structure bound to aPLs, however which conformation exists and predominates in solution remains controversial, and so is the conformational pathway leading to the bound state.
So, our investigation aims at highlighting the protein-protein-lipid interaction, molecular dynamics, and structural functionality at molecular level by biochemical assay, crystallography, smFRET and cryoEM methods to elaborate how ß2GPI binds to aPLs and how this complex behaves in solution and exerts their biological effects in antiphospholipid syndrome.