title: Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA.
abstract: BACKGROUND
  BAFF and APRIL are members of TNF superfamily. They play vital roles in the pathogenesis of autoimmune diseases. BCMA, a receptor, shows higher affinity for APRIL than for BAFF. Previous studies found that ligand binding specificity of BCMA may be determined by sequence outside DxL motif.
  
  
  OBJECTIVE
  Investigate the contribution of a segment outside the DxL motif of BCMA for binding with ligands.
  
  
  METHODS
  In this study, the conservative region of BCMA was divided into two segments: BCMA1 (NEYFDSLLHACIPC), a segment of the DXL motif and BCMA2 (QLRCSSNTPPLT), a segment outside of the DXL motif. Two peptides corresponding to the two segments were synthesized and their contribution to the ligands binding were detected by competitive ELISA. BCMA1-Fc fusion protein was also constructed, purified and analyzed by indirect and competitive ELISA.
  
  
  RESULTS
  BCMA2 had no inhibiting effect on the interaction of BCMA-Fc and BCMA1-Fc with BAFF, but, it inhibited 22.5% and 15.2% of the interaction of BCMA-Fc and BCMA1-Fc with mAPRIL respectively. The binding rates of BCMA1-Fc for BAFF were 91.7%, but 80.6% for mAPRIL, suggesting that BCMA1-Fc without BCMA2, bound BAFF well and less efficiently to mAPRIL.
  
  
  CONCLUSIONS
  These results suggest that BCMA2 outside of the conservative DxL motif of BCMA may play an important role in the binding selectivity to its ligands.
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Hao
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D020816:Amino Acid Motifs; D053264:B-Cell Activating Factor / Q000737:chemistry / Q000235:genetics*; D053301:B-Cell Maturation Antigen / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000737:chemistry / Q000235:genetics*
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D008024:Ligands; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: APRIL; BAFF; BCMA; BCMA1; BCMA2; binding mode; selectivity