Structural basis of BLyS receptor recognition.
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.
Oren
Deena A
DA
Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University, 679 Hoes Lane, Piscataway, New Jersey 08816, USA.
Li
Yuling
Y
Volovik
Yulia
Y
Morris
Tina S
TS
Dharia
Chhaya
C
Das
Kalyan
K
Galperina
Olga
O
Gentz
Reiner
R
Arnold
Eddy
E
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*
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