GRP78 and cell-surface GRP78 self-association; In silico perspective

Cell surface glucose-regulated protein 78 (cs-GRP78) was previously reported as a receptor of many infectious agents including viruses, bacteria, and fungi. The association of GRP78 inside the cell and at the cell surface is important to be studied to understand how the cell recognizes pathogens. Combined bioinformatics tools, molecular docking, and dynamics simulation were utilized to study the homodimeric form of GRP78 at both aqueous and impeded inside the lipid bilayer membrane. The results revealed that both systems are stable during the simulation period of 100 ns but the substrate binding domains α and β of one monomer of GRP78 have less fluctuations in the membrane system compared to the dimer at aqueous solution. This may explain the stability of the protein dimer inside the membrane. Additionally, we found that the GRP78 dimer in the membrane forms a stable pore of 12 Å diameter that remained open throughout the simulation period, indicating increased membrane permeability. This may explain the ability of cs-GRP78 to facilitate hydrophobic molecule internalization.