1MPV

Structure of bhpBR3, the BAFF-binding loop of BR3 embedded in a beta-hairpin peptide

Summary for 1MPV

• Entry DOI: 10.2210/pdb1mpv/pdb
• Descriptor: BLyS Receptor 3 (1 entity in total)
• Functional Keywords: beta-hairpin, protein binding
• Cellular location: Membrane; Single-pass type III membrane protein (Probable): Q96RJ3
• Total number of polymer chains: 1
• Total formula weight: 1593.92

Authors

Kayagaki, N.,Yan, M.,Seshasayee, D.,Wang, H.,Lee, W.,French, D.M.,Grewal, I.S.,Cochran, A.G.,Gordon, N.C.,Yin, J.,Starovasnik, M.A.,Dixit, V.M. (deposition date: 2002-09-12, release date: 2002-10-30, Last modification date: 2024-10-30)

Primary citation

Kayagaki, N.,Yan, M.,Seshasayee, D.,Wang, H.,Lee, W.,French, D.M.,Grewal, I.S.,Cochran, A.G.,Gordon, N.C.,Yin, J.,Starovasnik, M.A.,Dixit, V.M.
BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2.
Immunity, 17:515-524, 2002

PubMed Abstract: The TNF-like ligand BAFF/BLyS is a potent survival factor for B cells. It binds three receptors: TACI, BCMA, and BR3. We show that BR3 signaling promotes processing of the transcription factor NF-kappaB2/p100 to p52. NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells. Furthermore, wild-type mice injected with BAFF-neutralizing BR3-Fc protein showed reduced basal NF-kappaB2 activation. BR3-Fc treatment of NZB/WF1 mice, which develop a fatal lupus-like syndrome, inhibited NF-kappaB2 processing and attenuated the disease process. Since inhibiting the BR3-BAFF interaction has therapeutic ramifications, the ligand binding interface of BR3 was investigated and found to reside within a 26 residue core domain. When stabilized within a structured beta-hairpin peptide, six of these residues were sufficient to confer binding to BAFF.

PubMed: 12387744
DOI: 10.1016/S1074-7613(02)00425-9

Experimental method

SOLUTION NMR