Silva Joao H M da, Calmon-Hamaty Flavia, Savino Wilson, Hahne Michael, Caffarena Ernesto R
Laboratorio de Pesquisas sobre o Timo. Instituto Oswaldo Cruz. Fundacao Oswaldo Cruz (FIOCRUZ), Manguinhos, Rio de Janeiro, RJ, Brazil, 21041-250.
Protein Pept Lett. 2015;22(5):432-42. doi: 10.2174/0929866522666150302124953.
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.
“A增殖诱导配体”蛋白（APRIL）是一种在许多转化细胞和肿瘤细胞中过度表达的细胞因子，作用于肿瘤坏死因子B细胞成熟抗原（BCMA）以及跨膜激活剂和钙调节剂及亲环素配体相互作用分子（TACI）这两种不同的受体。我们在此通过详细的计算方法，借助分子动力学描述了TACI与其配体APRIL以及另一种结构相似的蛋白——B细胞激活因子（BAFF）之间的分子相互作用。动力学分析表明，TACI的R84和D85残基可能是候选突变位点，这会增加TACI与APRIL之间的亲和力。计算模拟、定点诱变和肽设计相结合可能是一种强大的工具，有助于推动更好的体外实验。我们的结果有助于阐明APRIL信号传导，并有助于通过使用特定肽来阐明阻断APRIL与其受体之间相互作用的效果。
