2gkw
From Proteopedia
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Key contacts promote recongnito of BAFF-R by TRAF3
Overview
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.
About this Structure
2GKW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Key molecular contacts promote recognition of the BAFF receptor by TNF receptor-associated factor 3: implications for intracellular signaling regulation., Ni CZ, Oganesyan G, Welsh K, Zhu X, Reed JC, Satterthwait AC, Cheng G, Ely KR, J Immunol. 2004 Dec 15;173(12):7394-400. PMID:15585864
Page seeded by OCA on Mon Nov 12 22:19:47 2007
