title: Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation.
abstract: 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.
authors.affiliation: Department of Biological Science, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Kyung Sook
authors.initials: KS
authors.lastname: Yu
authors.forename: Mi Eun
authors.initials: ME
authors.lastname: Lee
authors.forename: Dong Ryeol
authors.initials: DR
authors.lastname: Shin
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Ook Joon
authors.initials: OJ
authors.lastname: Yoo
authors.forename: Hayyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Jie-Oh
authors.initials: JO
authors.lastname: Lee
mesh_terms: 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*
chemical_list: 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