Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: The human B cell survival factor, B cell activation factor (BAFF), and its closely related homologue, a proliferation-inducing ligand (APRIL), modulate B cell functions by binding to three receptors, BAFFR, TACI and BCMA. APRIL binds more strongly to BCMA than to TACI while the opposite is true for BAFF. In addition, BAFF, but not APRIL, binds to BAFFR with high affinity. Both BAFF and APRIL are known to form homotrimers and heterotrimers, which display different affinities for their cognate receptors.
Methods: We used X-ray crystallography to determine the structural elements of the APRIL, BAFF and TACI binding sites.
Results: To understand the structural basis underlying the different binding affinities, we solved the crystal structure of the APRIL-BAFF-BAFF heterotrimer, either alone or bound to TACI.
Conclusion: Analysis of these structures and comparative analysis of previously solved structures of BAFF and APRIL in complex with BAFFR, TACI or BCMA revealed that the charged residues of BAFF and APRIL are crucial determinants of receptor binding affinities, conferring homotrimers and heterotrimers with a variety of signaling strength to modulate responses of immune cells.
To cite this abstract in AMA style:Jiang X, Tan T, Maskos K, Lammens A, Schneider P, Palinksy W. Co-Crystal Structure of TACI and APRIL-BAFF-BAFF Heteromer Suggests That Charged Residues in APRIL and BAFF Dictate Their Receptor Binding Affinities [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/co-crystal-structure-of-taci-and-april-baff-baff-heteromer-suggests-that-charged-residues-in-april-and-baff-dictate-their-receptor-binding-affinities/. Accessed January 28, 2022.
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