title: Structural basis of BLyS receptor recognition.
abstract: B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor (TNF) superfamily, is a cytokine that induces B-cell proliferation and immunoglobulin secretion. We have determined the three-dimensional structure of BLyS to 2.0 A resolution and identified receptor recognition segments using limited proteolysis coupled with mass spectrometry. Similar to other structurally determined TNF-like ligands, the BLyS monomer is a beta-sandwich and oligomerizes to form a homotrimer. The receptor-binding region in BLyS is a deeper, more pronounced groove than in other cytokines. The conserved elements on the 'floor' of this groove allow for cytokine recognition of several structurally related receptors, whereas variations on the 'walls' and outer rims of the groove confer receptor specificity.
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University, 679 Hoes Lane, Piscataway, New Jersey 08816, USA.
authors.forename: Deena A
authors.initials: DA
authors.lastname: Oren
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.forename: Yulia
authors.initials: Y
authors.lastname: Volovik
authors.forename: Tina S
authors.initials: TS
authors.lastname: Morris
authors.forename: Chhaya
authors.initials: C
authors.lastname: Dharia
authors.forename: Kalyan
authors.initials: K
authors.lastname: Das
authors.forename: Olga
authors.initials: O
authors.lastname: Galperina
authors.forename: Reiner
authors.initials: R
authors.lastname: Gentz
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
mesh_terms: D000595:Amino Acid Sequence; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha