2GKW

Key contacts promote recongnito of BAFF-R by TRAF3

Summary for 2GKW

• Entry DOI: 10.2210/pdb2gkw/pdb
• Descriptor: TNF receptor-associated factor 3, Tumor necrosis factor receptor superfamily member 13C (2 entities in total)
• Functional Keywords: cd40, nf-kb signaling, baff receptor, traf3, apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (Probable): Q13114
• Total number of polymer chains: 2
• Total formula weight: 24246.79

Authors

Ely, K.R. (deposition date: 2006-04-03, release date: 2006-04-11, Last modification date: 2023-08-30)

Primary citation

Ni, C.-Z.,Oganesyan, G.,Welsh, K.,Zhu, X.,Reed, J.C.,Satterthwait, A.C.,Cheng, G.,Ely, K.R.
Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation.
J.Immunol., 173:7394-7400, 2004

PubMed Abstract: B cell-activating factor belonging to the TNF family receptor (BAFF-R), a member of the TNFR superfamily, plays a role in autoimmunity after ligation with BAFF ligand (also called TALL-1, BLyS, THANK, or zTNF4). BAFF/BAFF-R interactions are critical for B cell regulation, and signaling from this ligand-receptor complex results in NF-kappaB activation. Most TNFRs transmit signals intracellularly by recruitment of adaptor proteins called TNFR-associated factors (TRAFs). However, BAFF-R binds only one TRAF adaptor, TRAF3, and this interaction negatively regulates activation of NF-kappaB. In this study, we report the crystal structure of a 24-residue fragment of the cytoplasmic portion of BAFF-R bound in complex with TRAF3. The recognition motif (162)PVPAT(166) in BAFF-R is accommodated in the same binding crevice on TRAF3 that binds two related TNFRs, CD40 and LTbetaR, but is presented in a completely different structural framework. This region of BAFF-R assumes an open conformation with two extended strands opposed at right angles that each make contacts with TRAF3. The recognition motif is located in the N-terminal arm and intermolecular contacts mediate TRAF recognition. In the C-terminal arm, key stabilizing contacts are made, including critical hydrogen bonds with Gln(379) in TRAF3 that define the molecular basis for selective binding of BAFF-R solely to this member of the TRAF family. A dynamic conformational adjustment of Tyr(377) in TRAF3 occurs forming a new intermolecular contact with BAFF-R that stabilizes the complex. The structure of the complex provides a molecular explanation for binding affinities and selective protein interactions in TNFR-TRAF interactions.

PubMed: 15585864

Experimental method

X-RAY DIFFRACTION (2.7 Å)