B-cell-activating factor (BAFF)/BAFF recepter (BAFF-R) complex
Homo sapiens (human)
B cells play a major role in the humoral immune response. Immature B cells in the bone marrow must undergo maturation in peripheral organs, particularly the spleen. There is a vigorous selection process during maturation of B cells and only a small fraction of developing B cells reaches maturity. BAFF(B-cell-activating factor) is one of the factors said to be important in this selection process. In vitro studies have shown that BAFF plays an important role in the survival of immature B cells called T2B cells. BAFF can bind to three kinds of receptors, BAFF-R, TACI and BCMA and BAFF-R seems to play a clear role in B-cell maturation.
These three kinds of receptors belong to the TNF receptor superfamily. The typical proteins of the TNF receptor superfamily have three or four cysteine-rich domains(CRDs) in their extracellular domains, and typically CRDs contain six cysteine residues that form three disulfide bridges which stabilize the elongated antiparallel beta-strands. BAFF-R, which contains only one CRD with four cysteine residues is an exceptional member of the TNF receptor family. The structure here shows the BAFF-BAFF-R complex. This icosahedral cage is composed of 60 BAFF and 60 BAFF-R monomers. Each BAFF monomer consists of a two-layered jellyroll beta-sandwich structure. Two neighboring BAFF trimers are in touch using an unusually long DE loop called 'flap' or 'handshaking' region. In the complex, BAFF-R binds to BAFF in a 1:1 molar ratio. The CRD of BAFF-R forms a short beta- hairpin structure, which may be stabilized by two disulfide bridges. The authors propose that an absolutely conserved Dxl motif located on the tip of the beta-turn is indispensable in the binding of BAFF.
Protein Data Bank (PDB)
author: Miho Higurashi