Title:Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA
Volume: 24
Issue: 6
Author(s): Chang Zheng, Xiaojuan Zhang, Zhen Zhao, Xiaofei Hao, Jing Wei*Jian Sun*
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
- Department of Molecular and Cellular Pharmacology, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072,China
Keywords:
BCMA, BAFF, APRIL, BCMA1, BCMA2, selectivity, binding mode.
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.
Method: 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.
Conclusion: 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.
