Molecular Dynamics Study On The Interaction Between Antigen Peptide And TAP Membrane Protein Molecule

Transporter associated with antigen processing(TAP)is a kind of heterodimerized ABC transporter,which selects antigen peptides derived from proteasomal degradation,translocates these peptide from cytosol across ER membrane to endoplasmic reticulum(ER)lumen,where peptides are loaded into major histocompatibility complex(MHC)class I molecules to be in turn released and exposed on the surface of immune cells,and triggers immune reaction.Along with the reveal of TAP gene and the role TAP plays in immune response as a dimerized protein,studies on relationship between TAP molecule and diseases step further.Recently,more and more researches prove that TAP molecule shows strong involvements in various chronic infection and autoimmune diseases.However,lack of 3D high resolution structure of full-length TAP,structures and functions of TAP molecule,mechanism of antigen peptides transport still are unknown.Here,we simulate the transport process and analyze interactions between TAP and peptide using steer molecular dynamics(SMD)with Pgp-based-TAP-model 2 based on homology modeling theory,and obtain structures of TAP-peptide interactions throughout the transport process.The state peptide binding to TAP is located after analysis on conformation changes of the system,with that structure,we find several residues play a key role in the interaction between TAP and peptide,with their surrounding residues,a hydrophobic pocket forms which provides anchors for C terminus of antigen peptides and coordinates the combination of peptides and TAP molecule.At the same time,we find antigen peptide experience a marked conformation change with comparison between structures of antigen peptide free and binding to TAP,which probably means peptides binding to TAP in a kinked conformation and in agreement with other researches.