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Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA

[ Vol. 24 , Issue. 6 ]

Author(s):

Chang Zheng, Xiaojuan Zhang, Zhen Zhao, Xiaofei Hao, Jing Wei and Jian Sun   Pages 489 - 494 ( 6 )

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.

Keywords:

BCMA, BAFF, APRIL, BCMA1, BCMA2, selectivity, binding mode.

Affiliation:

Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, 1Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, 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, Department of Molecular and Cellular Pharmacology, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072

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