Identify the key amino acid of BAFF binding with TACI

Abstract

B-cell activating factor (BAFF) has been used as a therapeutic target. To develop BAFF-specific small molecular inhibitors, it is necessary to know the key amino acid in the BAFF binding with its receptor. The key binding amino acid of BAFF interacting with its receptor TACI (trans-membrane activator and calcium modulator and cyclophilin ligand interactor) was analyzed based on the computer-guided molecular modeling method. According to theoretical prediction, a series of key amino acid mutants of BAFF, including M204 (Lys204 to Ala), M208 (Met208 to Ala), M209 (Gly209 to Ala), M210 (His210 to Ala), M234 (Gln234 to Ala), M236 (Met236 to Ala), and M237 (Pro237 to Ala) were designed and evaluated with biological experiments. The results show that M208, M209, M236, and M237 of BAFF were the key amino acids and in accord with the theoretical results. The results highlight clues for the further development of BAFF-specific small molecular inhibitors.