3K51

Crystal Structure of DcR3-TL1A complex

Summary for 3K51

• Entry DOI: 10.2210/pdb3k51/pdb
• Related: 2QE3
• Descriptor: Tumor necrosis factor ligand superfamily member 15, secreted form, Decoy receptor 3 (3 entities in total)
• Functional Keywords: dcr3, tl1a, tnf, tnfr, decoy receptor, immunity, cytokine, disulfide bond, glycoprotein, membrane, secreted, signal-anchor, transmembrane, apoptosis, receptor, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane ; Single-pass type II membrane protein . Tumor necrosis factor ligand superfamily member 15, secreted form: Secreted: O95150; Secreted: O95407
• Total number of polymer chains: 2
• Total formula weight: 40166.11

Authors

Zhan, C.,Patskovsky, Y.,Yan, Q.,Li, Z.,Ramagopal, U.A.,Nathenson, S.G.,Almo, S.C. (deposition date: 2009-10-06, release date: 2010-10-13, Last modification date: 2024-11-27)

Primary citation

Zhan, C.,Patskovsky, Y.,Yan, Q.,Li, Z.,Ramagopal, U.,Cheng, H.,Brenowitz, M.,Hui, X.,Nathenson, S.G.,Almo, S.C.
Decoy Strategies: The Structure of TL1A:DcR3 Complex.
Structure, 19:162-171, 2011

PubMed Abstract: Decoy Receptor 3 (DcR3), a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, neutralizes three different TNF ligands: FasL, LIGHT, and TL1A. Each of these ligands engages unique signaling receptors which direct distinct and critical immune responses. We report the crystal structures of the unliganded DcR3 ectodomain and its complex with TL1A, as well as complementary mutagenesis and biochemical studies. These analyses demonstrate that DcR3 interacts with invariant backbone and side-chain atoms in the membrane-proximal half of TL1A which supports recognition of its three distinct TNF ligands. Additional features serve as antideterminants that preclude interaction with other members of the TNF superfamily. This mode of interaction is unique among characterized TNF:TNFR family members and provides a mechanistic basis for the broadened specificity required to support the decoy function of DcR3, as well as for the rational manipulation of specificity and affinity of DcR3 and its ligands.

PubMed: 21300286
DOI: 10.1016/j.str.2010.12.004

Experimental method

X-RAY DIFFRACTION (2.45 Å)