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

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.

Cite this article as:

Zheng Chang, Zhang Xiaojuan, Zhao Zhen, Hao Xiaofei, Wei Jing*, Sun Jian*, Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA, Protein & Peptide Letters 2017; 24 (6) . https://dx.doi.org/10.2174/0929866524666170301115209

DOI https://dx.doi.org/10.2174/0929866524666170301115209	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305