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.
Kim
Ho Min
HM
Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Yu
Kyung Sook
KS
Lee
Mi Eun
ME
Shin
Dong Ryeol
DR
Kim
Young Sang
YS
Paik
Sang-Gi
SG
Yoo
Ook Joon
OJ
Lee
Hayyoung
H
Lee
Jie-Oh
JO
D000595:Amino Acid Sequence; D000818:Animals; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007074:Immunoglobulin G; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha