4KGQ

Crystal structure of a human light loop mutant in complex with dcr3

Summary for 4KGQ

• Entry DOI: 10.2210/pdb4kgq/pdb
• Related: 3K51 3MHD 3MI8 4EN0 4J6G
• Descriptor: Tumor necrosis factor receptor superfamily member 6B, Tumor necrosis factor ligand superfamily member 14, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: light, dcr3, tnf, tnfr, tnf14, structural genomics, psi-biology, new hvem, n-glycosylation, membrane, secreted protein, cytokine, ifn, jelly-roll fold, bind tnf receptor hvem and ltbr, ltbr, protein structure initiative, atoms-to-animals: the immune function network, new york structural genomics research consortium, nysgrc, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 74019.27

Authors

Liu, W.,Zhan, C.,Bonanno, J.B.,Sampathkumar, P.,Toro, R.,Nathenson, S.G.,Almo, S.C.,New York Structural Genomics Research Consortium (NYSGRC),Atoms-to-Animals: The Immune Function Network (IFN) (deposition date: 2013-04-29, release date: 2013-07-10, Last modification date: 2024-11-06)

Primary citation

Liu, W.,Zhan, C.,Cheng, H.,Kumar, P.R.,Bonanno, J.B.,Nathenson, S.G.,Almo, S.C.
Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly.
Structure, 22:1252-1262, 2014

PubMed Abstract: LIGHT initiates intracellular signaling via engagement of the two TNF receptors, HVEM and LTβR. In humans, LIGHT is neutralized by DcR3, a unique soluble member of the TNFR superfamily, which tightly binds LIGHT and inhibits its interactions with HVEM and LTβR. DcR3 also neutralizes two other TNF ligands, FasL and TL1A. Due to its ability to neutralize three distinct different ligands, DcR3 contributes to a wide range of biological and pathological processes, including cancer and autoimmune diseases. However, the mechanisms that support the broad specificity of DcR3 remain to be fully defined. We report the structures of LIGHT and the LIGHT:DcR3 complex, which reveal the structural basis for the DcR3-mediated neutralization of LIGHT and afford insights into DcR3 function and binding promiscuity. Based on these structures, we designed LIGHT mutants with altered affinities for DcR3 and HVEM, which may represent mechanistically informative probe reagents.

PubMed: 25087510
DOI: 10.1016/j.str.2014.06.013

Experimental method

X-RAY DIFFRACTION (2.27 Å)