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

Author(s): Chang Zheng, Xiaojuan Zhang, Zhen Zhao, Xiaofei Hao, Jing Wei*, Jian Sun*.

Journal Name: Protein & Peptide Letters

Volume 24 , Issue 6 , 2017

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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.

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Article Details

VOLUME: 24
ISSUE: 6
Year: 2017
Page: [489 - 494]
Pages: 6
DOI: 10.2174/0929866524666170301115209
Price: $58

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