In Silico Identification of Novel APRIL Peptide Antagonists and Binding Insights by Molecular Modeling and Immunosorbent Assays.
The "A proliferation inducing ligand" protein (APRIL) is a cytokine over-expressed in many transformed and tumoral cells acting onto two distinct receptors of the Tumoral Necrosis Factor B cell maturation antigen (BCMA) and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). We herein describe, through a detailed computational approach, the molecular interactions between TACI and its ligands APRIL and another structurally similar protein called B-cell activating factor (BAFF) by means of molecular dynamics. Dynamical analysis suggests R84 and D85 residues from TACI as possible mutation candidates, yielding increased affinity between TACI and APRIL. The association of computational simulations, site directed mutagenesis and peptide design could be a powerful tool, driving to better in vitro experiments. Our results contribute to the elucidation of APRIL signaling and help clarify the effects of blocking interaction between APRIL and its receptors through the use of particular peptides.
Joao H M da
JH
Silva
Flavia
F
Calmon-Hamaty
Laboratorio de Pesquisas sobre o Timo. Instituto Oswaldo Cruz. Fundacao Oswaldo Cruz (FIOCRUZ), Manguinhos, Rio de Janeiro, RJ, Brazil, 21041-250. savino@fiocruz.br.
Wilson
W
Savino
Michael
M
Hahne
Ernesto R
ER
Caffarena
D000595:Amino Acid Sequence; D000818:Animals; D053264:B-Cell Activating Factor / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D007163:Immunosorbent Techniques; D008024:Ligands; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects; D053303:Transmembrane Activator and CAML Interactor Protein / Q000737:chemistry / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D053264:B-Cell Activating Factor; D008024:Ligands; D010455:Peptides; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13