title: Structural analysis of the inhibition of APRIL by TACI and BCMA through molecular dynamics simulations.
abstract: APRIL (a proliferation-inducing ligand) is a member of the tumour necrosis factor (TNF) superfamily that binds the receptors (TNFRs) TACI and BCMA. Since it was discovered, a great amount of evidence has been reported about the involvement of APRIL in autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and multiple sclerosis (MS). In addition, an important role of APRIL has been described in different types of tumour cell lines and in a variety of primary tumour tissues where, in contrast with the normal ones, high mRNA levels have been detected. Accordingly, the design of compounds mimicking the inhibition of APRIL by its receptors appears to be a promising way to treat autoimmune and cancer diseases. As a first step to achieve these goals and in order to better understand the key interactions involved in these systems, we report a structural analysis of the inhibition of human and murine APRIL by its human receptors TACI and BCMA obtained by molecular dynamics simulations. Although most of the key interactions can be obtained from the existing experimental information, new described interactions between human APRIL and its receptors can contribute to a better design of APRIL inhibitors.
authors.affiliation: Department of Physical Chemistry, University of Barcelona and the Institut de Recerca en Quimica Teorica i Computacional (IQTCUB), Barcelona, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: González-Mendióroz
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Alvarez-Vázquez
authors.forename: Jaime
authors.initials: J
authors.lastname: Rubio-Martinez
mesh_terms: D000818:Animals; D053301:B-Cell Maturation Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D053303:Transmembrane Activator and CAML Interactor Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D053301:B-Cell Maturation Antigen; D046912:Multiprotein Complexes; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13