4MSV

Crystal structure of FASL and DcR3 complex

Summary for 4MSV

• Entry DOI: 10.2210/pdb4msv/pdb
• Related: 3K51 3MHD 4EN0 4J6G 4KGG 4KGQ
• Descriptor: Tumor necrosis factor receptor superfamily member 6B, Tumor necrosis factor ligand superfamily member 6, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: fasl, dcr3, tnf, tnfr, tnf6, structural genomics, psi-biology, new york structural genomics, research consortium, nysgrc, immunity, tnf supe cd95l, fas ligand, membrane, atoms-to-animals: the immune function network, ifn, jelly-roll fold, bind tnf receptor fas, protein structure initiative, new york structural genomics research consortium, cd95l, tnf superfamily, secreted protein, cytokine, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor ligand superfamily member 6, soluble form: Secreted . FasL intracellular domain: Nucleus: O95407; Secreted: P48023
• Total number of polymer chains: 2
• Total formula weight: 36505.57

Authors

Liu, W.,Ramagopal, U.A.,Zhan, C.,Bonanno, J.B.,Bhosle, R.C.,Nathenson, S.G.,Almo, S.C.,Atoms-to-Animals: The Immune Function Network (IFN),New York Structural Genomics Research Consortium (NYSGRC) (deposition date: 2013-09-18, release date: 2013-11-27, Last modification date: 2024-11-06)

Primary citation

Liu, W.,Ramagopal, U.,Cheng, H.,Bonanno, J.B.,Toro, R.,Bhosle, R.,Zhan, C.,Almo, S.C.
Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.
Structure, 24:2016-2023, 2016

PubMed Abstract: The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3.

PubMed: 27806260
DOI: 10.1016/j.str.2016.09.009

Experimental method

X-RAY DIFFRACTION (2.5 Å)