Abstract
TACI is a member of the tumor necrosis factor receptor superfamily and serves as a key regulator of B cell function. The extracellular domain of a typical TNFR contains multiple copies of CRD, which bind in the monomermonomer interfaces of a trimeric ligand. TACI binds to two ligands, APRIL and BAFF, with high affinity and contains two CRD in its extracellular regions, while BCMA and BR3, contain a single or partial CRD for binding the two ligands. However, TACI can be classified as a single CRD receptor because the amino-terminal CRD1 doesnt contribute to ligand binding. To obtain a new variant of TACI possessing higher affinities for binding, we fused a repeat sequence of CRD2 to the N-terminus of the short form of TACI. The new APRIL antagonist peptide, CRD2-shortTACI-Fc, was designed based on the modeling 3-D complex structure of TACI and APRIL. As expected, the purified recombinant CRD2-shortTACI-Fc fusion protein could bind to APRIL in vitro and demonstrated dose-dependent inhibition of APRIL-induced proliferative activity in Raji cells. We found that CRD2-shortTACI-Fc, has a higher affinity for binding to ligands than short-TACI-Fc, which contains a single CRD2.
Keywords: TACI, CRD2, BAFF, APRIL, affinity, autoimmune disorders, Novagen, DNA ligase, homology modeling, Pichia pastoris
Protein & Peptide Letters
Title: Expression and Characterization of a Variant of TACI (CRD2-shortTACIFc) in Pichia pastoris
Volume: 19 Issue: 3
Author(s): Rui Wang, Shiliang Zhou, Xiaomin Peng, Xin-Wen Zhou, Zhi-Qun Xie, Yuxiong Wang, Wei Mo and Min Yu
Affiliation:
Keywords: TACI, CRD2, BAFF, APRIL, affinity, autoimmune disorders, Novagen, DNA ligase, homology modeling, Pichia pastoris
Abstract: TACI is a member of the tumor necrosis factor receptor superfamily and serves as a key regulator of B cell function. The extracellular domain of a typical TNFR contains multiple copies of CRD, which bind in the monomermonomer interfaces of a trimeric ligand. TACI binds to two ligands, APRIL and BAFF, with high affinity and contains two CRD in its extracellular regions, while BCMA and BR3, contain a single or partial CRD for binding the two ligands. However, TACI can be classified as a single CRD receptor because the amino-terminal CRD1 doesnt contribute to ligand binding. To obtain a new variant of TACI possessing higher affinities for binding, we fused a repeat sequence of CRD2 to the N-terminus of the short form of TACI. The new APRIL antagonist peptide, CRD2-shortTACI-Fc, was designed based on the modeling 3-D complex structure of TACI and APRIL. As expected, the purified recombinant CRD2-shortTACI-Fc fusion protein could bind to APRIL in vitro and demonstrated dose-dependent inhibition of APRIL-induced proliferative activity in Raji cells. We found that CRD2-shortTACI-Fc, has a higher affinity for binding to ligands than short-TACI-Fc, which contains a single CRD2.
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Wang Rui, Zhou Shiliang, Peng Xiaomin, Zhou Xin-Wen, Xie Zhi-Qun, Wang Yuxiong, Mo Wei and Yu Min, Expression and Characterization of a Variant of TACI (CRD2-shortTACIFc) in Pichia pastoris, Protein & Peptide Letters 2012; 19 (3) . https://dx.doi.org/10.2174/092986612799363136
DOI https://dx.doi.org/10.2174/092986612799363136 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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