Structural characterization of a Protein A mimetic peptide dendrimer bound to human IgG.

摘要: Understanding the chemical physical properties of protein binding sites is at basis rational design ligands. The hinge region Fc fragment immunoglobulin G an important and well characterized site, known to interact with several natural proteins synthetic Here, we report structural evidence that a Staphylococcus aureus Protein A mimetic peptide dendrimer, deduced by combinatorial approach, binds close Cgamma2/Cgamma3 interface constant human IgG1 molecule, partially hindering site. X-ray analysis evidenced primary site located between terminal Arg residue ligand peptidic arm hydrophobic consisting Val308, Leu309, His310. molecular dynamic model derived from structure showed in water room temperature complex further stabilized formation least one more contact second carboxylic group amino acid, such as Glu318, Asp312, or Asp280. It appears thus stability Fc-dendrimer determined synergetic multiple bonds different nature dendrimer arms accessible sites. electrostatic van der Waals energies were monitored during MD simulations confirmed energetic two interactions.