Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation
Copyright policy )Crystal structure of the BAFF–BAFF-R complex and its implications for receptor activation
B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 A. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a beta-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the beta-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI-BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.
- Korea Advanced Institute of Science and Technology Korea (Republic of)
- Korean Association Of Science and Technology Studies Korea (Republic of)
- Chonnam National University Korea (Republic of)
- Korea Advanced Institute of Science and Technology Korea (Republic of)
Models, Molecular, Protein Conformation, Molecular Sequence Data, NECROSIS-FACTOR RECEPTOR, Crystallography, X-Ray, B-LYMPHOCYTE STIMULATOR, Receptors, Tumor Necrosis Factor, MEMBER, Mice, B-Cell Activating Factor, Animals, Humans, Amino Acid Sequence, AUTOIMMUNE-DISEASE, BLYS, Conserved Sequence, T-CELL ACTIVATION, Sequence Homology, Amino Acid, Tumor Necrosis Factor-alpha, TACI, 500, Membrane Proteins, MICE, Immunoglobulin G, TNF-RECEPTOR, Sequence Alignment, FACTOR FAMILY, B-Cell Activation Factor Receptor
Models, Molecular, Protein Conformation, Molecular Sequence Data, NECROSIS-FACTOR RECEPTOR, Crystallography, X-Ray, B-LYMPHOCYTE STIMULATOR, Receptors, Tumor Necrosis Factor, MEMBER, Mice, B-Cell Activating Factor, Animals, Humans, Amino Acid Sequence, AUTOIMMUNE-DISEASE, BLYS, Conserved Sequence, T-CELL ACTIVATION, Sequence Homology, Amino Acid, Tumor Necrosis Factor-alpha, TACI, 500, Membrane Proteins, MICE, Immunoglobulin G, TNF-RECEPTOR, Sequence Alignment, FACTOR FAMILY, B-Cell Activation Factor Receptor
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